A very warm welcome to the Novo Nordisk 2024 Capital Markets Day. My name is Lars Fruergaard Jørgensen, and together with my management team, I'm very excited about hosting all of you here today. We're excited because of our unprecedented growth. We're excited about the strategies, the progress we're making in building capacity, expanding our pipeline to sustain a very attractive growth going forward. And, this is obviously all about serving more patients, and we believe we can serve many more patients in the future. We would like to start the meeting by actually inviting an individual who has been on in one of our trials, to learn a bit more about what it means living with obesity and also heart failure. So Isabelle Davis, please join me here on stage. Please.
Thank you.
So, Isabelle, thank you so much for, for joining us today and, accepting to share a bit with us, your experiences. And I would like to ask you by, helping us to understand what does it mean to live with obesity and also heart failure?
Well, I was very overweight, and initially you just put down the breathlessness to being overweight, and not being able to do very much. But however, when I got diagnosed with heart failure, I realized that the weight was exacerbating things.
Mm.
So yeah, I mean, simple tasks like going upstairs. By the time I got to the top of the stairs, if I got to the top of the stairs before I started getting out of breath, really quite breathless.
Mm.
Doing simple chores around the house. Could only do so much, and then need to sit down and get my breath.
Yeah.
Yeah, it was-
You also described to me how the pandemic did not help.
Pardon?
You also described to me how-
That is right.
... COVID-19 did not help that at all.
Of course, when the pandemic hit, the coronavirus hit us, you became much more sedentary. So you were sitting about a lot more in those days. And then, as I said, when you start to move about, you-
Yeah.
I was feeling, as I said, very breathless.
So then you had an opportunity of being enrolled in-
That's right
... our STEP HFpEF trial. So-
That's right.
What happened there?
Well, I went for an echo, and got told that I had heart failure, and I was asked if I would take part in a drug trial, which, having been overweight most of my life and tried various diets, I said yes right away.
Mm.
I would, I would do this, I would try it.
Yeah.
I started on the trial in 2021.
Yeah.
Mm-hmm.
What, what happened when you got enrolled to the trial?
Well, I was monitored pretty closely, which was a good thing. Especially when you get told you've got heart failure, you're kinda quite taken aback at that because you don't think about things like that. When I went on the trial, I was going monthly to the hospital to get to partake in the medication, and very quickly, I saw a weight loss.
Mm.
So by the end of the trial, I had lost a lot of weight. You know, I just think along the lines of, think of your suitcases when you're carrying 30 kilos.
Yeah.
That's more or less what's come off me, and I couldn't lift 30 kilos now, but I was walking about with that.
Yeah.
So...
Yeah. So how has being on-
Well, I-
the trial changed your life?
I go upstairs, and I'm not having to stop at the top of the stairs and go, and go like that.
Yeah.
When I went shopping, I'd maybe get halfway around the shop, and I think I've had enough.
Yeah.
But now I can... I just go, and I finish my shopping, and do more household chores that I didn't, you know, wasn't really able to, to do to the same degree that I can now.
Yeah.
Last year, my granddaughter was over from Australia with her two little girls, aged two and four. It was nice 'cause we could go to the park with them-
Yeah
... which was really nice, being able to help with the children. My granddaughter left myself and the other granny to look after the children for a day. So that was good that-
You told me they are-
We were able to do-
... aged 2 and 4-
2 and 4
... so that's a bunch to keep,
Yes
... control.
Yes.
Yeah.
Whereas I don't think I would have coped-
Yeah
... before with all that weight on.
Yeah.
So yeah.
So, when you think about your life today-
Mm-hmm
... and the alternative, so how do you think it has changed your life?
Oh, I think it's made a great difference. Unfortunately, though, I had a hip replacement last year, and I've been recovering from that. So, I don't think I would have got the hip replacement to begin with because I had such a lot of weight on. I would have had to wait and still be in pain. So this year is a new year for me, and I feel as though a new lease of life.
Yeah.
That I'm looking forward to better weather in Scotland, which is not often happens. So that I, you know, I can get out more.
Yeah.
Yeah, and be more active.
... Isabelle, thank you so much for sharing your story with us.
Not at all.
It's a great inspiration for all of us working in Novo Nordisk.
Mm-hmm.
I can promise you we'll keep on-
Yeah
... doing research and-
Well, I'll be 78 this year.
Yeah.
I feel as though I've got a new lease of life.
Good.
With that-
Thank you so much.
Okay, thank you.
Thank you. Thank you, Isabelle. Okay. Thank you, Isabelle, for sharing that story with us, and I could not think of a better way to actually start a Capital Markets Day, and a better way of bringing our purpose to life, which is really to drive change to defeat serious chronic diseases. And, we live at a time with aging populations, more and more people living with one or more chronic diseases, like we heard, Isabelle tell about. And this is turning into the biggest, say, cost burden for the healthcare systems. And in many healthcare systems, around 80% of the cost burden is actually linked to these chronic diseases. So this is the strongest and the most motivating purpose I could think about for a company. The purpose is in the center of our strategy.
It's surrounded by the Novo Nordisk Way, stimulating how we work in Novo Nordisk, our culture, our values, and a commitment to being a sustainable company. I'll get a bit back to this later on. Our strategy, our corporate strategy, remains the same. It's striving for leadership or expanding leadership in diabetes, obesity, rare diseases. And then the change on the slide is that we have reworded other serious chronic diseases; it was not so motivating to be other into cardiovascular disease and emerging therapy areas. And we also do that change because we're very pleased with how we are actually shaping up our pipeline in cardiovascular disease, and we look forward to sharing that with you later on today. I would also say from a corporate strategy execution point of view, we are very pleased in how we are executing on our strategy.
We see a strong growth, we see a pipeline shaping up, and we are tracking in expanding our manufacturing capacity. So you can say that our strategic aspirations for 2025 is serving us very well in guiding our strategic execution, and based on that, we are not going to change our strategic aspirations today. They'll expire end of next year, and we do not see it as meaningful to change them this time about. We do acknowledge that we have achieved two of the aspirations: our diabetes aspiration of getting to above one-third of the market. We have checked that. It doesn't mean that we're holding back. We think we have tremendous growth opportunities sustained in diabetes. And we've also achieved the aspiration of getting to more than DKK 25 billion in obesity sales. And again, it doesn't mean that we're stopping there.
We think we have a tremendous runway in obesity. So, the strategic aspiration serves us well, and they stay as they are. The key focus for us is to do what is on this slide, and I actually showed that slide last time we had a Capital Markets Day. So really sustaining the growth opportunity we have based on semaglutide across a number of therapy areas. We have a wealth of clinical data solidifying our position, both in diabetes and obesity, and we see a very, very strong opportunity for driving sustained growth there. In parallel, we are also building breadth of pipeline to further accelerate and sustain growth in the coming years from these new areas. So in essence, what we are solving for here is really to strengthen and broaden our pipeline.
It's to build the capacity needed to bring these products to many more patients going forward, and it is to evolve the organization to support that innovation and scaling of the company. You can say this is really the essence of the Capital Markets Day. This is the agenda for today. We'll unfold a bit more of the corporate strategy, then we'll go in and do a deep dive on where are we in research and early development. We will address how we're building capacity, and then we go into deep dives on our therapy areas, and we have breakout sessions, where we look at some of the markets in a bit more depth. We're also going to unfold how we you know seek to bolster the company performance and innovation based on digital tools, artificial intelligence.
We wrap up with financials, growth in the markets, the P&L, and return to our shareholders. So this is the plan for today, and we have put in Q&A sessions around the agenda, so there'll be ample opportunity for you to engage with us. We will, throughout the day, be making forward-looking statements. I think you know this slide by heart, so please be careful. What we preach from stage might turn out to be different, so please pay attention to these forward-looking statements. You'll see this slide a number of times, but we'll only talk to it once, so that was now, so now is to take it to heart. With that, I would like to invite Dave Moore to stage. Dave Moore is Executive Vice President of Corporate Development. You might recognize Dave.
Dave worked in NNI, our U.S. operations, as head of commercial some years back. Left to explore a career in biotech and private equity, but came back a year and a half ago to lead our corporate strategy and business development activities. So over to you, Dave.
Thank you, Lars. Thank you. Thank you. Such a pleasure to be back at Capital Markets Day, and really happy to kick things off and spend some time with you to talk about our corporate strategy. As Lars mentioned earlier, our purpose is the center point of our corporate strategy. It's anchored there, and we're here to defeat serious chronic diseases. It's what drives us. For people like Isabelle, who we just spoke to this morning. We have four focused areas that comprise our corporate strategy. Diabetes and obesity are the number one priority. Diabetes is our heritage. It's where it all started, and we will continue to be the leaders in diabetes into the future. That includes both Type 1 and Type 2 diabetes. We are also the leaders in obesity. We have been since the beginning. That is not going to change.
We will strengthen our leadership position in obesity, and we will shape the future obesity market. In our rare disease franchise, we also have a position of strength. We've been in these businesses since the 1970s and 1980s, and we will use that position of strength, that strong history, to expand to the new areas as well. As Lars mentioned, cardiovascular disease is now a new focused therapy area, and we've put extensive work into building a competitive pipeline in cardiovascular disease. It's an adjacency. It aligns well with our history in diabetes and obesity. And we're also working on some emerging therapy areas, such as chronic kidney disease and liver disease. So when we execute on this strategy, it goes right back to our purpose.
We're now at a point where we're adding millions more patients every year that we're serving, like Isabelle, and that is what will continue to drive us into the future. One thing that has served us well over our long history is a clear and focused strategy, and that will continue. That's the way we operate. And we wanted to share with you some of the, some of the considerations, some of the choices that we make when we think about our focus areas, when we think about our strategy into the future. So on the left, what you see here is the external view. The things that we take into account when we're thinking about moving into an area or strengthening our position. We have to understand: what's that market look like? Where's the real potential, the value that exists? Is it growing?
Are we able to participate in that growth, and can we lead? Secondly, is there a real need? Is there a place in therapy that we can own differentially to compete? Once again, our focus is to be a leader if we go into an area. And then lastly, what's the level of risk? What's the level of innovation that's required? We are an innovation-based company. If an area doesn't require new innovation, it doesn't really line up with who we are and our history. And then what we do is we take those external views, and we marry them up with our company. As you see, we, we don't go into areas that don't work for Novo Nordisk. Where's our position of strength? Do we have strengths that we can leverage to compete in that marketplace? Our internal capabilities, what's our R&D capability in that area?
Can we supply the market? Is our commercial execution at a place that we can leverage that strength as well? What happens when we work through these considerations is we have a good understanding of where we will play and how we will win in the future. We believe strongly that strategy is about making choice. We can't be everything to everyone. We must prioritize. This is what it looks like when we prioritize, even within our focused areas. As we mentioned, diabetes and obesity, priority number one, and will remain that way for some time. We wanted to give you some words to characterize what does that mean to be the top priority here? Well, from an investment standpoint, it means that's our key investment area. It means the most time, energy, resource will go into those therapy areas.
It also means if you think about the R&D pipeline, it's broad, it's also deep, so that we understand the future segments, we're shaping that and where these diseases are going into the future. The second priority is now cardiovascular disease and rare blood disease. What that looks like is we want to go after multiple targets in the key segments within those therapy areas. The investment focus is we're building competitive pipelines for the future. So those future launches take these therapy areas to the next level. The third priority is the emerging therapy areas, MASH and chronic kidney disease... as well as rare endocrine disease. So this is a little bit more targeted, a little bit more focused. We're looking for those synergies that exist within the organization, those adjacencies, when we're building pipelines for these therapy areas.
And lastly, when we do work in indications like Alzheimer's disease, Parkinson's, these are not focused therapy areas for us, but they're still important diseases with a high unmet need, and that is a targeted investment where we're really looking for opportunities. It's trigger-based, based on, on how those programs progress. So when we take our focused areas, and now we think about it in terms of an R&D pipeline, we then break that down into near-term and long-term focus. And if you think about near term, it's really about executing on the strategy. That's, that's our focus, right? So if you take each one, in diabetes, what's our near-term focus? Maximize CagriSema and maximize insulin icodec. That is near term, right in front of us. In obesity, it's also about maximizing CagriSema. We really like it when one of our programs can serve more than one therapy area.
In cardiovascular disease, it's about maximizing ziltivekimab, and in rare blood disorders, it's Mim8. Those are very clear. The long-term focus on the bottom is about building those pipelines for the future, and here is where that work really matters. Where's this therapy area going? How do we see it evolving? What's the competitive landscape? Let's take obesity as an example. What will it take for us to be the leader into the future? What's the innovation height that we're going to need to bring? What do those future market segments look like? That's what we think about in terms of the long-term focus. I also wanted to spend a couple of minutes to share some insights and thoughts around external innovation. As you've seen over the last couple of years, our BD M&A activities have increased, and you should expect that to continue.
It will continue in a focused way, just like we've been talking about. We're looking for research and development stage assets that we can add to the pipeline, where our internal R&D capabilities can add value. That's what makes sense to us. We have dedicated search and evaluation teams for each one of these therapy areas, that are out there looking for that opportunity that we can add to the pipeline that complements our internal R&D capabilities. We have a pretty high bar internally. We're looking for things that are better, that are in modes of action, that are different than we might be working on. In addition, we look for technology platforms that we can leverage across these TAs, and that work will continue into the future.
So now we've given you an idea of where we focus, the choices that we make, and then also how we're building for the long-term growth. I'd like to turn it back over to Lars.
Thank you, Dave. And in my opening, I mentioned that I would just get a bit back to what it means to be a sustainable company. So before we get into R&D and manufacturing capacity, just allow me a few slides to address this. So I mentioned that we're committed to being a sustainable company. We are very pleased with our ownership structure. We have the ultra long perspective from the foundation being a safe anchor for the company, and we have, in addition to that, the day-to-day, say, discipline that the capital market puts us on. I think that's a very, very attractive ownership structure. Our shareholders have, in our articles of association, adopted the triple bottom line principle.
So we have to be a socially responsible company, we need to be an environmentally socially responsible company, and obviously, a financially responsible company. We'll get into the finances later on today, so allow me just a few comments on how we look at the social and environmental responsibility, starting with the environmental impact. We have committed to be, say, a net zero company by 2045. We're progressing on that. We have a commitment to be also zero in our emissions from our own operations and transport by 2030. Short term, we are building a lot, and we're growing a lot, so that has an impact, but doesn't change our long-term commitment to this agenda.
We are proud about how we have taken initiative to actually deal with the waste that come from use of our devices. We have the Returpen program, where we're now live in four countries, where we take back plastic devices for recycling. And since this is a bigger challenge than just one company, we've also invited our competitors and peers in, and we're glad to see that more companies have joined this effort. We're now increasingly focusing on biodiversity. I personally feel this is a bigger challenge for society than CO2 emissions, which perhaps can be solved by innovation. So it's important for a company like Novo Nordisk to focus on what is our biodiversity impact, and how do we mitigate that? From a social responsibility point of view, obviously, our largest contribution is the innovation we provide to patients.
But when you look at access and the fact that we treat now a bit more than 40 million patients, it's good to understand that close to 7 million of those are actually benefiting from some kind of access program from Novo Nordisk. There's a lot of focus on the African continent and access to medicines. So I'm also pleased that we have formed a partnership with Aspen Pharmacare to bring local filling of insulin vials to Africa, something that can be scaled and reach many patients in the coming few years. And we're also tracking and helping more than 50,000 children living with Type 1 diabetes in getting access to free insulin, and those children would have a quite difficult life unless we had provided that.
Prevention is also on the agenda. You can say, dealing with obesity is actually preventing Type 2 diabetes, but we're also looking at, say, the broader societal aspects. We have now 47 cities involved in our Cities Changing Diabetes program to, you know, drive health benefits in these big cities. We have renewed our partnership with UNICEF, and we have established an Obesity Transformational Prevention Unit last year. So these are some of our elements of our social commitment. I'd like to finish up on compliance and ethics. I know it's something that's been a keen focus area for many of our investors. So just, you know, share with you that when we look at the Novo Nordisk Way, a key element is actually compliance are key.
So we guide all our people to follow ten essentials. One of them is never to compromise on quality and business ethics. It's involved in our code of conduct. It's involved in all the training efforts we do. We do audits, we do trending and risk management of all of these aspects. And of course, when you approach a new disease area like obesity with some inherent dilemmas, this becomes even more important. So we have taken initiative to both communicate to healthcare practitioners in what is the correct use of our medicines according to label.
We have done a lot of work in making sure that our employees are clean, keenly aware of how do we interact with HCPs, how do we interact with stakeholders, even when we bring a patient on stage here, and what can we talk to as a company. We have beefed up resources, so as we increasingly roll out our obesity portfolio in various countries, there'll be dedicated people to secure that we stick to compliance. So, as the CEO, I just wanted to make you hear from me honestly that I'm very comfortable in the program we have. It does mean that there'll not be mistakes from time to time, but I feel we have a really, really strong compliance program.
So with that, we'll close the strategy session, and I would like to invite Marcus Schindler, our Chief Scientific Officer and EVP of Research and Early Development to the stage. So, Marcus, it's over to you.
Thank you, Lars. Great to be back after two years and in a full room, and to all of you out there, good morning, good afternoon, good evening. A lot of things have happened. A lot of things have changed over the last couple of years. What hasn't changed, as Dave and Lars have said, is our aspirations, right? They hold true because they talk a lot about pushing the boundaries. They talk a lot about as, innovation, providing meaningful impact to patients in large chronic diseases. I think that is actually sort of our Northern Star here, that we're following in research and early development, and we're spearheading this because our core job is to generate data, make new hypotheses, make new molecules, and test those. This is how it all starts.
And we do this, of course, and I think Isabelle was a fantastic reminder that on an individual level, A, we make impact, but B, the job is far from done. 20% relative risk reduction still means that 80% are untreated. So there's a significant unmet medical need in the big chronic diseases we're working in, and on a population scale, on a global scale, the numbers are rising. And probably as I speak, the numbers I have here on the slide are already out of date. Just a couple of days ago, a publication, The Lancet, you know, estimated the number of obese people in the world, including a staggering number of adolescents, to be in excess of 1 billion, way outperforming malnutrition as the number one issue on the globe. Right?
But you, of course, know all of this. So how field we're working in, but I think Dave has also said very nicely, "It's one thing to know where we want to play, but how can we be uniquely positioned actually to make a difference in this?" So how do we in research and early development actually translate those corporate priorities, our corporate strategy, the unmet medical needs that we're seeing into reality, and how do we actually run R&D? We are, we maintain, but we will also continue to drive leadership in diabetes and obesity. There is no doubt in this. And I often get asked, so are we, are we at the end of innovation with obese- with, with, insulins or, or, GLP-1s? And the answer is, of course, no.
This field, you know, while it has a tremendous success, was even seen as the breakthrough of the year by the Science magazine. You know, it's still at the beginning scientifically, and there are many more things we can learn from, and I'll share a little bit about this later on. But there's also to be said, to go beyond those two molecular classes, which have served us and the patient population well. Novel mode of action, driving actually down in different biological pathways, which are complementary, or that might actually uncover entirely new biological paradigms in the diseases we're working in. And it is about not only losing weight or lowering glucose, it is about achieving outcomes.
And I would already, at this point in time, you know, highlight that, for us, it is really important to take this conversation beyond weight. A staggering number of data through a lot of outcome trials where we show that people live longer, healthier, and better lives. And I think this is all what matters at the end of the day. So it means also understanding and dealing better with comorbidities and outcome endpoints that we're maybe not yet addressing fully. And one thing I think, which I know is high on your radar, but most certainly is on our radar, so and how can we turn this from interesting scientific discovery, from molecules or even therapies that are suitable for a few million patients, to an entirely scalable version?
Henrik will touch on this, but it is actually in the molecular design when we're starting our programs that we're now thinking about: Is it scalable? How can we ever get to tens or hundreds of millions of patients with the chemistries that we're dealing with? So that, for us, is the next innovation hurdle or barrier or actually, sort of a stimulating factor for all our scientists that we go after. At the last CMD, I spoke about the concept of human-centric drug discovery. So really focusing on the one species that is relevant for us, the one species that we would like to treat. Today, I can share with you some really exciting news on how we're working with this.
We've nearly tripled our investments in access to human databases, to human cohorts, and those cohorts actually are relevant for obesity, diabetes, cardiovascular, and other diseases, kidney diseases. But very deliberately, we are also dealing with a larger diversity, ethnicity, a global setting where we simply want to learn more about the people around the globe and whether there are commonalities or differences in the disease etiologies and potentially the treatment, opportunities that we can see. So that remains an important cornerstone for us. And why is this even relevant today? Because we now can interrogate large data sets. With this immense rise in computing power and sophistication, we're actually able to unravel very, very complex systems.
For those of you who've signed up to the digital and AI breakout session this afternoon, we'll give you concrete examples, but also talk to you how the quality and the access of data, and how we actually deal with data also in a compliant and ethical way, are fundamental to everything that we do. It's, of course, not enough to have access to the data and to interrogate them, but how do we actually turn data into knowledge? What systems are we actually using to move those to new drug projects?
This is actually what we call the Target Discovery Engine, which is a composite of a platform that interrogates large data sets, so through computing power, through artificial intelligence, but it is also a system where we use human model system, microphysiology systems, in vitro systems, when we can and when we need, to actually test those new hypotheses. So we start with human data, and we interrogate those human data through human systems, and then we validate our targets. And why is that a good thing? Because it will give us better targets, have higher confidence that they will make a difference in late-stage clinical development in Martin Lange's organization. Just one year in action with the Target Discovery Engine, we have nearly doubled the number of projects and targets that we actually have progressed through this.
This is honestly just the beginning because we have designed this engine, this machine, as being entirely scalable. So we are thinking about interrogating thousands and thousands of targets and actually fast-tracking them onto the clinic. So this is something we can do with publicly available databases, where we join consortia and some other groups. But there's one particular data set we are very, very excited about, and that is, comes obviously from our own SELECT trial. 5-year data on cardiovascular outcome in the patient population that matters to us. 17,000 people were in this trial, and we have an opportunity, of course, analyzed and blinded, to interrogate those data. And those data point can be genetics, they can be blood biobank samples, and actually from 11,000 of those, we even have proteomics data available to us.
And that is a not only rich source of information, it is actually a unique proprietary, and we feel, you know, competitive advantage to us to have this data set. And what are we gonna do with this? First of all, of course, from a scientific discovery point of view, it's, it's very interesting to see what actually happens because we have longitudinal data points. What happens with treatment? What systems are changing? Which molecules are contributing actually to semaglutide's effects on those phenomenal outcomes? It will help us also to understand disease progression, maybe also different patient subpopulations, but it will unravel novel biological systems and thus novel targets for us. So an incredibly rich source. So the first pillar is where we look into human data externally available.
The second pillar is we look into human data through our own clinical trials, SELECT being the first one out of the block. The third pillar for anything that we do, novel disease understanding, but also novel targets, is through partnerships. And I would say we've come a long way over the last couple of years, and I won't read through all the numbers, but it's an impressive cadre of collaborations, different co-collaborations around the globe, where we talk about new biologies, new modes of actions, fundamental biology, but also a significant number of those partnerships actually delivering to the pipeline. And this is a nice opportunity for me also to give you a nice glimpse and insight into what we do in cardiovascular and rare disease.
With Heartseed, we're working on a cell therapy product for heart failure, where we generate cardiomyocytes and inject those into the heart of patients with severe heart failure. That trial, that phase I, started some time ago, and that trial is actually ongoing. 2seventy bio, formerly bluebird bio, we are collaborating on a gene therapy approach for Factor VIII . Really excitingly, we've achieved in primates a proof of concept where we could see relevant, physiologically relevant levels of Factor VIII being produced through this gene therapy. So we're very excited, of course, to take this into humans soon. Inversago, our cannabinoid receptor inverse agonist, I'll spend a little bit more time on in one minute, but let me also speak to Ventus, where we work on the inflammasome, the NLRP3 inhibitors.
This is actually a very important fundamental node in biology, where many inflammatory pathways come together, and we believe that potentially blocking this pathway could have therapeutic benefit. We see this in the greater franchise of what we're already doing with ziltivekimab on IL-6. It has potential in cardiovascular disease, MASH, but obviously also other opportunities here with this exciting biology. So let me spend a few minutes on the cannabinoid receptor system. Why are we actually excited about this? And wasn't there something there that didn't work out so well a few years ago? Absolutely, and that is all true. What I think is fantastic here, we have a very clearly formulated, differentiated hypothesis for this new class of molecules that the company Inversago has discovered and developed. And what did they do?
They realized, obviously, there are cannabinoid receptors in the brain, they regulate some of our reward system, but there are actually more cannabinoid receptors throughout the human body. And they seem to play a role in kidney disease, in cardiometabolic disease, and other important physiological systems. So what if we could actually selectively target the-- these classes of cannabinoid receptors, you know, that are beneficial without potentially running into those side effects that we have seen in the past, which were of psychiatric nature? And they, with laser precision, actually designed those molecules to do exactly this, and this brings us to a very exciting class of molecules. Monlunabant, INV-202, is already in clinical trials, and Martin will touch on this in a minute, and how we're also progressing with this.
Very exciting for us that there's also and it does look promising. There's a follow-on compound, 347, that you see on the right-hand side, which we have in-depth profiled in our preclinical species. And I hope you agree with me that the weight loss we're seeing here, in this particular species, in excess of 30%, is promising. So we would like to show with this follow-up compound, you know, more efficacy probably than what we already have, and potentially also working on a different pharmacokinetic profile. So it's not just a single molecules; it's a class of molecules. And through this acquisition and partnership even, we're really exploring this space and continue to be excited about this. Last time, we spoke about Dicerna. Actually, two times ago, we spoke about the Dicerna partnership.
So it's a red line here whenever I come, so from partnership to acquisition, and now we're actually fully integrating this platform. This is the siRNA platform that gives us unique access to intracellular targets. And as a reminder, it helps us actually to target genes with extreme precision. We'll knock out the genes that we want to knock down and nothing else. And the very cool thing is, that effect actually usually lasts for a significant long time, months, quarters, and even longer. We've made significant investments over the last couple of years in CMC, but also into the platform, and that will actually enable us to not only work on, as it has previously done, liver targeting through the GalNAc system, what they call the GalXC platform, but actually go beyond liver targeting.
You might remember that was our aim, that we target different tissue types in the human body, and we call this the GalXC+ platform. This platform actually is a collection of different chemistries for different target organs. So why is that important? Because now we can actually make those molecules target specifically a gene of interest and then deliver it actually to the target organ of interest with high precision. Right? The first one of those molecules are actually now out of the block. Just to remind you, Dicerna, even before we acquired it, to this very day, has delivered 11 first time in humans. The platform is de-risked. So it's really why we see this as one of our core elements now.
We now have also our very first siRNA launched onto the market, Rivfloza, and we're now also seeing the first extrahepatic targeting moiety is already in clinical trials. So we have a lot of confidence in this platform, even to say that 50% of our pipeline will actually be about non-liver targeted moieties. It'll make a big impact to our pipeline. 50% of our own siRNA projects will be in obesity and diabetes, and I think now we're seeing actually the beauty of integrating this, because now the unmet need, the deep biology expertise in obesity, diabetes, and other some serious chronic diseases, comes at play and is combined with this platform. And that actually also keeps us confident that we're already in play with what we see as an average annual 3 first time in humans.
So this becomes our workhorse of intracellular precision medicine. And that leads me to this overview of platforms that we're using, and why is that important? Because at the end of the day, we do not want to be limited too much when we see novel targets, when we see exciting biology, that we don't have the right tools in hand. We're now broadening our toolbox, and of course, we come from an extremely strong heritage on protein and peptide therapeutics, and we continue to innovate in this space, and that will stay like this. There's much more to be done. We were the first ones out of the block with all biologics, and we're leading the way. You'll hear later on this afternoon actually, how we are changing from antibodies to mini binders. You know, totally changing molecular formats.
That, of course, is applicable in all our therapy areas. We see siRNA having a similar potential, and that makes us really, really confident, also to further invest in, into this. Cell therapy, I gave you the one example on cardiomyocytes, on heart failure. Our Parkinson's trial with a partner, Lund University, is actually ongoing, and we continue to work on our beta cell program, which is actually a collection of different programs to tackle this really, really big problem. We have a small but significant number of small molecules now in the pipeline from discovery, but also to late stage, including phase III, and, you know, Henrik can touch on that as well.
It is not yet our core, but we are actually committed to gain expertise, knowledge, and depth into this particular molecular entity to be a significant player in this. And then we're actually starting to get serious about gene therapy, gene editing. We're using R&D as a platform to experiment here. Obviously, also with an aim to see, are those technologies one day suitable for larger patient populations? So consequently, that has actually impacted the distribution of modalities of our pipeline. As you can see on this slide here, siRNA takes a bigger chunk than just a few years ago, and so do small molecules. And that is actually a really nice distribution that we're seeing here. It helps us to tackle as many targets as possible.
Sometimes it also helps us actually deploy different technologies and modalities to the same target, and then we'll find out which of those modalities is actually best. Could be an siRNA, could be an antibody. Yeah, and I think that flexibility is very, very useful. And of course, all of this is enabled through our ability to interrogate those targets and technologies in a much faster way through automation and through in silico capabilities. The pipeline, consequently, has significantly grown. This is just the number of net projects, so to speak. We obviously also have the diligence to stop projects if they don't fulfill our criteria, and our bars are incredibly high. They're incredibly high.
So whatever makes it, you'll see on this graph here, you see diabetes and obesity still being a sizable portion, and that will remain so and will continue to provide breadth and depth, but cardiovascular and rare blood disorders play a more significant role than before. Let me just give you a short, quick deep dive into some of the programs that we have, in particular in diabetes and obesity. In diabetes, one of our must-win battles continues to be glucose-sensitive insulin. I shared last time that we have achieved the first human trial. We actually showed that our concept proved to be true. We could also show that we have a different approaches and chemistries to actually tackle this very, very serious problem.
So that remains a big, big, important piece for us, to be working on, and the next molecules are coming out of the block now. Infrequent dosing, in particular in diabetes, but also in obesity, are big topics for us, and we're excited about a once monthly. It's early, it's in phase I. A once monthly GLP, GIP, combined molecule. It's actually a single molecule, where we feel that will add significantly, to convenience. In obesity, I spoke briefly about, the Inversago molecules, the cannabinoid receptor molecules, oral amycretin. And you, of course, will remember, this is a single molecule that combines efficacy and, and affinity to the amycretin, to the amylin receptor, as well as the GLP-1 receptor.
Yeah, and this, this molecule, we have first tested in an oral presentation utilizing, the, the SNAC platform and as a once daily oral. But why we're actually really excited about amylin, why do we believe that amylin is a, is a key competitive edge for us? Because it's not an incretin. It is a hormone, but it's actually released from beta cells in the pancreas. And the interesting thing when we look at it, actually, GLP-1 and amylin act in concert. They work together. They're, they're entirely complementary, not only what we see on weight, on glucose, but potentially also on other interesting comorbidities. And you, of course, are fully aware of, the, the data we've generated with, with CagriSema....
So the question for us was, what if we not only had two molecules in one syringe, but actually had a single molecule combining those two pharmacologies? We might actually get to a point where we see, you know, significant weight loss, and then those potential benefits of amycretin, as I've shown you on the right-hand side, also on lean body mass. And let's start with the efficacy data. So in 12 weeks of amycretin, we actually saw a body weight reduction of 13.1%. So we believe that is actually not only competitive and interesting, but it actually also confirms everything that we have predicted that we saw, both from animal species, but also what we know about the combination of amylin and GLP-1 in a single molecule.
There was nothing new, and that is the good news in terms of side effects. We've seen things which are entirely consistent with two classes, and we also see a very benign pharmacokinetic profile. And Martin will actually get later on into how we're actually taking onward CagriSema, both in diabetes and in obesity. So these are the kind of data, really interesting, exciting data for us when we push the boundaries of science. So you'll see us to continue to do, as Dave has said, maximize the GLP-1 franchise, learn more about GLP-1, make better molecules, make less frequent dosing, more scalability, maximize the value in incretin and amylin biology. One example I gave you here. All right?
And then actually build out a broader pipeline on novel mode of actions, biologies that we don't even understand yet, to really push the boundaries of science. Within the next 12 months, you will see us pushing a new tri-agonist, three different biologies that we're exploring in a single molecules into first time in human testing. So we're very excited about this, and we see very, very promising preclinical data. We'll continue to innovate on amylin, because we're absolutely not done here. I don't have so much more to learn. One great example, you also hear in the breakout session, this afternoon, and you'll see a new, amylin molecule also in clinical testing throughout this year.
And then, of course, we turn our attention to not only managing food intake and energy expenditure, but also looking into weight maintenance, the importance of lean body mass preservation, but I would actually say rather than lean, I would say functional body mass, and then how we can do this in a sustained, but also from a portfolio point of view, sustainable way. And that is very important. So all these investments in the portfolio, the new science that we're tackling, the target discovery engine, and our cutting-edge technologies and leadership in biology and in obesity and diabetes, actually leads us to continuing our aspiration on tripling the first human doses. Had a good year last year and even better the year before, and we'll continue this growth in 2024 and 2025.
So that actually gives you not only, I hope, a status of where we are today, but actually also what you can expect from us in the coming period. We'll continue with our core capabilities and technology and science, but we also grow those. We have unique tools to do this. And the new frontier for us is really to think about how we take this out to many more patients. So scalable as a new innovation, scalability, and that is probably a good segue over to Henrik Wulff. Thank you very much.
Thank you, Marcus, and good morning or good afternoon on where you are in the world. So, advanced molecules, broadening the toolbox, more complicated molecules, you need to stay very alerted when you are in a manufacturing, in particular, when you combine that with the number of patients that we want to serve. So it should actually be a dialogue up here, with Marcus. And I will have to say, these days, being working with manufacturing development and manufacturing in this company, the requirements around that is that you stay very alerted. You are very interested in what is going on already in preclinical, in phase I and in phase II, because if you're not prepared, then you will not reach the many patients we want to reach.
So you saw the numbers of insulin patients, diabetes patients, and Marcus also showed the number of obesity patients. The combination of what they're doing in R&D, actually early research and development, and what we are trying to do in manufacturing, is to take all the complications, all the advanced molecules, and make it as simple as possible, because that served more purposes. And I will come back to that. I also have forward-looking statements. So just to start with some perspectives of how we are doing in the scaling part. And we have actually served 5 million more patients in just one year, last year. That's by far the most, the highest growth of patients in Novo Nordisk ever in one year. How can we do that?
I brought some simple numbers on the right-hand side. We are increasing our organization significantly. We have moved, in just two years, from 16,000 employees to 25,000 employees in just manufacturing. They need to be trained, they need to be educated, they need to fulfill cGMP requirements before they go into operations. We do this worldwide, all sites. It's not a trivial task. Secondly, we have now scaled our CapEx organization so that they, in 2021, could handle DKK 6 billion in CapEx investments a year. Now, in 2023, they could handle DKK 26 billion, and you saw the number for this year, and I will come back to that later. We have moved the number of Ozempic pens.
We have moved that three times up since 2021, and our API manufacturing output, here we just picked semaglutide, I think it's relevant for you, that's four times up in two years. So there is a significant scaling ongoing. And then you also know that, the announcements, and I'll come, I will come back to that, you also know the announcement of our CapEx programs that we have done last year. They, they are, of course, not in operations already now, so they are part of our future scaling. Let's talk about volumes. We are the clear leader in the world in diabetes volume. We are the clear leader in the world in diabetes GLP-1 volume. We are the leader in obesity GLP-1. How do we do this, and how do we plan to continue this? We have more than 50 years of experience in high-scale API manufacturing.
We have used many, many years of experience to build, to optimize, to utilize existing knowledge into new products and new molecules. It's a very, very important task that you keep this vehicle running in everything you do in manufacturing, because the key is, in particular, if you base your product on our existing platforms, then we are up to a head start when you continue your growth. So in particular, within API, it's process industry. Many of you will go to the site tomorrow. You will get a glimpse of what we are doing. You will be impressed. And this is the example of accumulated, accumulated experience in our, in our business, how we have worked with this so that we can scale even faster and even bigger with smaller footprints. We are not done with the API. The API needs to go into something.
So, the biggest platform that we have is fill-finish glasses, liquids. We have a significant installed capacity worldwide on cartridges and vials, and we are building the syringes. And you also know we started a few years ago with actually moving our semaglutide API into a tablet technology. We have also, for many, many years, been producing our own devices and scaled our own devices in different generations. So, we have noticed the interest about volumes and scaling, so we will focus on that. But I'll just have to say, manufacturing and scaling and volume is nothing without product quality and compliance. So that's very, very important. It starts with patient safety, it starts with product quality, and it starts with living up to the expectations on cGMP regulations that are ever increasing.
So that's also a game. The last part of the game is having a sound and ever-improving productivity. Why? Because first of all, it served the financial circulation of funding to back to Martin Lange and Marcus' area in research and development, bringing innovation height even higher up in Novo Nordisk. Secondly, of course, it's a competitive edge of manufacturing, having the lowest possible unit cost with the highest possible quality. Our manufacturing, it looks pretty smart when you see it on a slide like this. It looks like we designed it this way. It's of course a evolution. It's also evolution, and you all know this is a Danish-based company. We started the business in Denmark. We have kept on expanding our capabilities in the country.
So we have a massive presence of API manufacturing in Denmark. We have 3 sites producing API for our products, and then lately since 2015 we started planning expansion in North America, so there we have 2 sites. We have by far the largest platform on yeast. That is the platform that we use for diabetes product and obesity products... then we are actually the media are not paying that much attention to that, but we have actually a quite a significant expansion ongoing for cardiovascular and emergent technology capacity also here in Denmark also on API. So that's also important, and it speaks back to what Marcus talked about, the potentials of other platforms than yeast. So we are also expanding that. Then we have E. coli and synthesis that we also need to use.
The CapEx investments are focused on scaling API, and we will continue optimizing those with better yields and expansions. Another important task here is that when we sneak around and listen to the R&D folks, what they're doing, it's really important to try to get it into the installed capacity and the expansions that we are doing. And what we try to do is to build in flexibility, so that one example is that we cater for whether the company wants to use the capacity for the oral compounds, or they want to use the API for the injectables. It's even more important when the next generations of obesity medicines kicks in. Then from API to fill-finish, our global footprint is now expanding due to our wish to buy the Catalent sites, three Catalent sites.
We are now expanding from 11 sites to 14 sites. They are placed across the world, and now we now we colored them a little bit, so you can see where the Catalent sites are placed. But all the sites that we have already, they're all expanding. The newest site that we have is our Ireland site that we actually bought for tablets. We have both manufacturing development people there, but we also have manufacturing there. We also intend to expand that, both for our oral semaglutide tablets, but also for example, Inversago. So we have we have expansions ongoing all places. We try to balance this so that we have regional supplies, and we are serving as close as possible to the markets.
Let me just talk to the three Catalent sites. There is one major site in Indiana, in U.S. There is a smaller site in Belgium, and there is a significant site in Italy. Why do we want to buy these three sites? So first of all, the sites, they are already operating. So for us, that means that in this case, there's 3,000 well-trained employees already in the sites. They speak the same language as us. We can talk manufacturing, we can talk optimizations, we can talk cGMP compliance. The buildings are there, well-maintained, and they're operating. This is, of course, a significant advantage compared to pick a greenfield somewhere in the world, starting finding the people, starting finding the construction, and then start from there.
So that is what we, what we want to do with these three sites. And it's also important to repeat, and we also said that in the announcement, we do not plan to interfere with the contracts already in these sites. These sites are going to serve the existing contracts to the existing customers in the sites. Our plans are made on top of this, so that's important. Finally, from fill-finish to the patients, there is some significant elements in choosing the right devices and choosing devices or platforms to scale. So now I just took some well-known pictures of devices. So from the left-hand side, you see our well-known connected durable device for insulin patients.
So I only need to produce one of these for a full year, full year consumption, because they get the cartridge, and they get the medicine. The vials, normally, they are designed so that you need one per month. Our FlexPen is also approximately one per month because the cartridge is designed so it can take four doses. Then comes the famous single-dose device, that's one dose, and in obesity medicine nowadays, it's one dose, one week, and then you throw it out, the whole thing out. And of course, the tricky part here is how to scale this and what to select if you want to scale your opportunities.
So it's really important, back to Marcus's presentation, that the molecules are designed so that they can be scaled, but it's also important that the delivery systems are chosen, both, absolutely both from an environmental point of view, from a CapEx point of view, but of course, also, please remember, the patients, they need to stack these pens up in the fridge. So the smaller it is, the better it is for everyone. We will step up our CapEx investment, of course, also in this area to follow the pace of the API expansions. We will, in this case, utilize CMO partnerships. That is not possible in the API space. We are the only one producing this kind of API, but in this field, there is many people out there you can team up with that can help you producing.
We will try to push, again, together with R&D, for less frequent dosing. And again, in this area, we will do whatever we can to design and build for flexibility in case that we change direction over time. What does it sum up to? There's a very simple overview of how we are trending in our CapEx program. We have doubled the program from 2021 to 2022, from 2022 to 2023, and then we have also almost doubled it from 2023 to this year. So, I can tell you, and you will also see that in Kalundborg tomorrow, those of you that are going there, there is major activities ongoing many, many places in Novo Nordisk. We've just summed up our announcement.
You see, many of these are within API until now, and of course, fill-finish will follow. Please be reminded then, when you're using DKK 45 billion in CapEx in one year, then you are not done in that year. So it takes a significant time to build advanced manufacturing, get it validated, get it approved, and it's not only one approval. We want worldwide approvals. We want approvals for all the countries in the world, so you need to go through all the countries and all the authorities to get the factories approved. That's very important. Sometimes you forget, why don't you just build a factory and then produce? You cannot do that in pharma. You need to get it approved, the products and the facility.
Then, if we take another look, and we take on the most famous brands that we have, then you will notice on this slide, and that's what I try to illustrate here, is that we intend to use the same manufacturing technologies, the same setup, across these drugs on API. So Rybelsus, Ozempic, Wegovy, soon to come, CagriSema, potentially amycretin, we plan to use the same setup, the same type of manufacturing technologies for these kinds. So there's major synergies in getting this right from the get-go. On the below side of the slide, we are still expanding our tableting technologies and capacity. We are, of course, expanding our FlexTouch. That's our main pen for Ozempic and Wegovy. We are expanding our single-dose device for, in particular, Wegovy in U.S.
We are now designing our dual-chamber pen for the launch of CagriSema, and then we will continue utilizing our existing device platforms. So when you look at this, one thing that you need to take away is that we are extremely disciplined in trying to get as many as possible compounds, medicines, and opportunities for Novo Nordisk into the same API systems, because that holds a major advantage within scaling, regulatory approvals, competencies, et cetera. And then we are more flexible on our fill-finish and on our devices to basically scale. Final slide. We have used 100 years in Novo Nordisk to get to around 40-42 patients.
With the CapEx plan that we have in place, the understanding of the potentials of the molecules and the brands in the market, the patient reach, the relevance in the market, our abilities to scale, we are planning to serve significant more patients the next period. So what you need to take away from this session is that we, we believe that we have the expertise, the scalability within biologics. We think that's a significant competitive advantage for Novo Nordisk. We will continue our CapEx investment programs to serve the potential that we have in the market, the many patients, and certainly also to move even earlier in the R&D pipeline to make sure that we serve a broader and bigger Novo Nordisk, also from a science point of view. We have plans in place now for serving many more patients in the next period.
Thank you. And then, I will invite for a QA, Q&A session with those that has already been on the scene, including the CFO now.
That's important.
That's very important.
Good morning. I see a good energy here, a lot of people raising their hands. So with limited capacity, then I think we'll have to do it based on some house rules. So we'll do 15 minutes of Q&A. So now it's for you to work. And please state your name, and please restrain yourself to one-
... question per person. So we go with the sun. The sun is almost out. It's Denmark, it's March. So we go from the window here. So, yeah.
Morning, Rajesh Kumar from HSBC. Just on the CapEx plans, thanks for explaining how you're scaling up. If you could give us color on how fungible the investments are to next generation products, like when you move from, you know, Ozempic to, say, CagriSema, can you still be able to use the same facilities? And within that piece of question, you mentioned that the Catalent plants will continue providing to the existing customers, you know, the contracts. When the contracts end, can they be repurposed?
There was 2 questions.
So there's two questions. So we are very disciplined here.
With the supply.
Which one do we want, number 1 or 2?
The first one.
Okay, the first one.
The first one?
Can I-
Yes.
Flexibility in our factories.
Yes, we have our eyes on CagriSema, of course, because that's the next generation of obesity medicine in Novo Nordisk, and we can use the same facilities.
Great. So, we move here. Seamus?
Thanks. Seamus Fernandez from Guggenheim Partners. So really the question is on that scalability question, and the way that amycretin can actually slot into the subQ formulations over time. It seems like that's something that can move very easily into the overall FlexPen device over time. So just wanted to get a better sense of that strategy.
So-
Yeah.
So I-
Yeah, so now we are close to the forward-looking statements because we are very early, right? So that's important, but the way that we see it right now, it's actually exactly the same answer as before. We think we can use the same facilities and the same devices that we are scaling right now.
All right. Thank you, Henrik. Then we move to Pete.
Thanks, Peter from Citi. One question. The last slide, Henrik, you've—you're starting with 40 million patients, and we know the market's gonna be a billion. If we took an illustrative—you have illustrative on the, on the slide, if we took that away, I mean, we all know you're going out to supply to hundreds of millions, but the scale of your ambition in terms of how much of the market you can supply, any ballpark figures you could give us there would be helpful.
Yeah, we have not prepared for that question, right, Karsten? We have prepared for that question. So, I will try to give you the most flavor that I can because the products are also different. So it's also a matter of which product we decide to produce in the facilities. Let's assume that we have the box that we have now announced. So that's important. There's some... For me, there are some differences. What is the strength? What is the yields? And et cetera, et cetera. But it's still within the same sort of ballpark. You probably all know the dynamics between oral and injectables, but let's just talk about the injectables. And then I'm back to my slides with the missing figures.
What we are doing here, because, of course, we have all seen now the potentials with obesity, that is, we are taking the accumulated knowledge that we have in all the facilities that we have within insulin, and then we have redesigned the whole thing so that, on the same footprint, we can scale much higher. That's our plan. What it leads to is that, depending on the sort of the portfolio of the products that we decide to put in the facilities, and, of course, also the scalability of the equipment.
Great. I think that's as clear, close as you get, Pete. So, then, then we go to-
I can, I can feel how they look at me.
Sachin.
Sachin Jain, Bank of America. A question for Marcus on the amycretin data you've put up. I'm sure you're expecting this. So questions on what's not on the slide. So what dose is that data at? And could you flesh out the safety in any more detail relative to CagriSema? And then I just wanted to be super clear on the profile you interpret. To us, it looks like a little bit better than CagriSema, which was, I think, 10% at 12 weeks, and a decent chunk better than Lilly's orforglipron, which is about six or seven. Just wanted to confirm my understanding is correct. Thanks.
Yeah. Whether that classifies still as one, but let's talk about amycretin. So obviously, we'll share much more detail on amycretin, actually on the molecule, but also on the trial and what we know preclinically, in due course. So you'll get a deep dive on this. What you see here is obviously what makes us really excited in terms about the dose. As you know, it is really hard to compare across trials and how long, you know, patients have been on top doses and so forth. But all I can say is we feel, A, this is a very competitive profile. B, the slope of the curve looks promising. So at this part, at this juncture, no sign of plateauing.
And third, and maybe also as a scientist, that makes me really comfortable. It fulfilled nearly all the predictions that we made from preclinical and everything that we knew from CagriSema and the individual components. Yeah, so percentage points up or down, we feel this is in a really, really good place. And keep in mind, for the first time, we combined here two separate entities into a single molecule. You know, and additivity of these effects was not necessarily given when we set out to design the molecules. So we're very, very pleased with what we're seeing.
Great. Thank you, Marcus. Then we move to Marcus .
... Thank you. A question on GLP-1 fill finish. Catalent has provided some a roadmap, effectively going from a unit of 1 to roughly 7, 23-26, and then doubling that, so going from 1 to 7 to 14 units of fill finish capacity behind GLP-1 medicines by 2030. Could you help us understand your own ambitions using those three steps, and how important you are, how reliant you are on Catalent to make that progression? Thank you.
Yeah. Yeah, like, plans for Catalent.
Yeah.
Customer commitment, and, then we-
Yeah-
Build up from there.
... First of all, customer commitments, and we have been in looking at that, and we have also been in to see what is the potential of these facilities compared to how we run our own facilities 24/7. And they will play a part of our capacity build, also a significant part of it. That includes, and that's why we can fulfill the customer's obligations in there. That, of course, includes that we are installing more equipment in those facilities. And the technology that we are moving in is the same technology as we are moving in across our own sites. So there, there's no sort of... It's a linear flow.
If you take the whole sort of global picture of fill finish that we look at, whether it's CMOs, whether it's the Catalent side, whether it's our internal expansion, you see a fill finish that will follow API expansions.
Right. Thank you, Henrik. Then it's, Michael. Wait, can we have a mic, too? Yeah.
Thank you. Michael, Michael Novod from Nordea. Maybe for Marcus on, on the technology that is used for the once monthly GLP-1 GIP. Is that sort of a also universal technology that could potentially be applied also to a once monthly incretin?
So, we are exploring a number of infrequent dosing for us, I mean, maybe to start back, infrequent dosing for us, I think is an important area because we feel actually that will open up a new innovation space. And whether it's once monthly or beyond, I think we'll need to see. So one thing is obviously we have different technologies, right? With siRNA, for example, it is in the core molecules that we see very long-lasting effects. When we have incretins, obviously, we're using different chemistries than to prolong those effects of those incretins.
We are obviously very interested, and maybe that is the core of your question, in technologies that are suitable for a number of key molecules out there, that if we wish to do so, you know, we can deploy this technology. And, you know, those technology investments for us will take precedence over just solving for a single problem.
Thank you. Then, we move around the table to Martin.
Martin Parkhøi, SEB, and for Lars, maybe on one of the first slides of the day with the illustrative graph of the sales development long term, could you elaborate a little bit on your thoughts behind the development of semaglutide post the LOE? What is your thought process? Is it due to, you know, Henrik's job or whatever?
No, but it's clear that, I think we have one of the perhaps largest categories ever in, say, the pharmaceutical world, both in terms of number of patients, but also in terms of number of units to be produced. Bear in mind, as long as we look at injectable therapy, these are highly complex presentations in high volumes. When you start mapping the world, there are very few products like that. It actually takes a lot to serve those patients. We feel that, we'll probably see a long period in front of us where we'll be launching these products. The classical modeling of, say, four or five years of uptake, plateau, and then decline, I believe will be much different for molecule like semaglutide.
It would take, say, a disruptive technology to change that, and I don't see that around the corner. We'll be building a capacity to cater for many more patients going forward. We believe we are the best-suited company for also serving those patients after a loss of exclusivity.
Thank you, Lars. Then this is a very active table, Richard?
Thanks, Karsten. Richard Vosser from J.P. Morgan. Maybe one back on amycretin. I saw at the top of the slide the format of oral and subcutaneous, I think, at the top of the production slide for amycretin. So just to confirm that you'd be looking to move both formats forward. It seems very good as an oral, but obviously flexibility with an injectable. But just to confirm that. Thanks.
So, there you'll have to hold your breath until Martin Lange comes on stage in some of the later sessions. Sorry about that. So we go to Simon.
It's enough.
Okay, Florent, you take it, and then we move back to Simon.
Good morning. Thank you. Florent Cespedes from Société Générale. A quick question on the monthly GLP-1 GIP. Do you see anything different on safety and efficacy profile, and could you use this platform for maintenance treatment? Thank you.
It's too early to say, to be honest, whether there's anything untoward. We don't expect this, of course, but, you know, it's early clinical testing, so, we would be monitoring. You've seen on my slides that I think weight maintenance is one of the three dimensions, I think, for innovation. One is efficacy, the other one is scalability and sort of weight maintenance, quality of weight loss, are important elements for us. So anything that is infrequent and makes it easy for patients and/or prescribers actually to do this, I think is certainly in play.
... Thank you, Marcus. Simon?
Thank you. Simon Baker from Redburn Atlantic. Another one for you, Henrik, on sema. You very helpfully gave us indexed levels of API capacity at two time points. I wonder if you could give us the same indexed levels on semaglutide yield. So where are we - where were we before? Where are we now? Where could we go to? And just as a point of reference, where is mammalian yield compared to yeast? Because that's the most likely route by which biosimilar competition will come in, rather than trying to emulate your yeast process. Thanks so much.
So Simon, before, before Henrik start out, then we'd rather not get into detail on specific yields. So Henrik, perhaps if you can, speak about the platforms and why we believe that the yeast-based platform is highly competitive, generally speaking, for proteins and peptides, and our approach, vis-à-vis yields on the mammalian platform also.
Thanks, Karsten, you just saved me. So, I'll give you another perspective, actually, because the interesting part of us expanding quite heavily, both on the mammalian platform and on the yeast platform, is actually we run it the same way. Meaning that the technologies and our base core competencies, we use that both within mammalian and within yeast. So one data point is why do we expand mammalian capacity in-house when there's so much mammalian you can buy? Because it's too expensive to buy compared to my unit cost. So that's also about yields. And it just show that our technology and the way that we operate these technologies in large-scale, continuous API manufacturing, they are quite competitive.
Even if there is installed capacity out there only on mammalian, not on yeast, we still are expanding ourselves, and we are and now with the new products coming in from R&D, also within cardiovascular, that is a competitive advantage for us. And if you... Sorry for the long answer. Anyway, so if you combine the sort of the buildup on the unit cost and the full manufacturing cost, then API is our core technology, and the scaling of the API is a smaller part of an injectable medicine, no matter what we use it for. So that's my answer on yields.
Thanks, Henrik. And then, we move to... Yeah. Yeah.
Hi. Thank you. Steve Atkins with Polen Capital. I'm curious, as semaglutide continues to expand usage, what you've learned about patient adherence and how to improve patient adherence, whether through devices or patient education?
I think we'll get a bit-
Yeah
... back to that later, won't we?
Yeah. Let's take it under the TA sessions. So now we'll have to do the final question for this session because we all need a break. So last question here.
Hopefully, it's quick. Hi, Emily Field from Barclays. On amycretin, you've long said that the bar for amycretin is CagriSema, which I've interpreted as good as. Based on the data that you've seen in the phase I thus far, do you think it can now be better?
Yeah, I wouldn't want to speculate on phase I data. As I said, you know, to a previous question, we feel it's in a very competitive place, and it's really consistent with what we've expected. So obviously, you know, another cliffhanger here, Martin will share with you really exciting progress, how we take it actually through clinical development onward. And I think then we have much more solid data to, at the end of the day, answer your question.
We don't set bars for efficacy, so-
Yeah.
Great. Thank you, Marcus. That concludes this part of the agenda, and now it's time to stretch legs. It's 15 minutes, catch management if you didn't get the answers to all your questions, and then looking forward to be back on the TA sessions. Thank you.
Thank you.
It's all about your mindset. In my home country, Kenya, 15,000 people die every year because of diabetes. My name is Kuresha Nur , and I want to change that. Living with diabetes is not easy. It is very complex. Without insulin, I cannot survive. I come from a marginalized Somali community where girl child education is not considered important, and I was discriminated because of my diabetes. Some people say that I cannot do anything. That includes getting education, going to school. I decided to prove them wrong and kill the stigma around diabetes. So I have started a community-based organization in Mombasa called the Diabetic Champions, where I empower young girls with diabetes to make them believe that they can become champions in their own life.
So welcome back from the break, and now we're going to move into the therapy area sessions. We'll start with diabetes, where we have the longest history, but we will talk to you about how we are going to continue to expand our leadership, both from a commercial execution point of view, but also from a pipeline point of view. And we will start, of course, with taking a look at our current leadership. You remember we set the targets last set. We've already met it. We are not going to stop here. We will continue to innovate in this space, and we also will talk to you about our commercial execution. The problem with diabetes is still huge. As you will recall, today, 1 in 10 million—1 in 10 has diabetes...
In the future, we expect that it will be one in eight. It's not just living with diabetes that it is, is the problem, it's actually also the comorbidities that are related to diabetes. You see here that it results in a life expectancy that is eight years shorter. We also know that around 30% of people living with T ype 2 diabetes are also affected by cardiovascular disease. If we take chronic kidney disease in its broadest sense, we know that 40% of people living with Type 2 diabetes are affected by, uh, chronic disease, uh, chronic kidney disease as well. The unmet need is still huge, and there's a lot more we can do. To Marcus's point, innovation is not over in this space at all.
Looking at our leadership, you see that we have expanded it to 33.8% of total diabetes. This is of course primarily driven by our GLP-1. The GLP-1 of total has actually doubled in the last few years, as you see here on the right-hand side. And this is, of course, primarily driven by the fact that GLP-1s can address not only sugar levels, but also cardiovascular risk, especially with Ozempic. You've seen the results, but of course also a very convenient treatment that is a once-weekly treatment. So, we are going to continue to expand our leadership into these segments. We are looking to explore innovations that goes beyond just HbA1c, also more into the cardiometabolic space, as you heard earlier from Marcus.
We are also going to look at how we can do preventative, potentially in the future, curative treatments. The prevention starts with obesity, knowing that obesity is the leading cause of Type 2 diabetes. Of course, we are also going to work with digital solutions, how we can support patients, making it a lot easier to live with Type 2 diabetes, but also Type 1 diabetes when it comes to more intelligent devices and when it comes to also supporting dosing regimens. On the right-hand side, you see how we are competing with very significant brands, very well-known and recognized brands, both in the oral space, in the injectable GLP-1 space. Then we, of course, looking forward to launching the world's first weekly insulin in not too long from now.
We look forward to expanding also further, and Martin will talk to that in the future, into each of these segments with our, with our innovations and further developments of the pipeline, as you see. But let's just dig into, one of these innovations, icodec, for a moment. When we look at icodec, we know that there is a huge potential in the basal segment. It's the biggest of the insulin segments. We have a market share around 30%, and we know that there is a potential of around DKK 40 billion in this segment. We expect, as you see here also, that icodec can make a real difference in the dynamic segment. The dynamic segment is basically, people who are new to basal treatment or people who are willing to switch.
When we are asking physicians and patients whether a once-weekly insulin that has slightly better efficacy but, and comparable safety, whether that is interesting, we get very strong answers to that. That's, that is certainly very interesting. More than 80% of physicians would say that just the once-weekly approach to insulin is a reason to change insulin. So we expect that this dynamic segment will continue to expand from the 30% that it is today, to an even more dynamic segment in the future because of the advantages of a once-weekly insulin. We know also from patients that it's very cumbersome to be treated on a once-daily regimen. And of course, while it's not exactly comparable to GLP-1s, we know that once-weekly just have many advantages for patients.
And here we have seen from our trials, slightly better efficacy and similar safety, which is, of course, very relevant when it comes to insulin. The other focus we have is, of course, on the GLP-1 and expanding into more, you can say, of the comorbidities related to Type 2 diabetes. Here you see what we call a Venn diagram, and you will get all of this later, so you don't have to write down all the numbers in the bubbles. But what we will show you throughout the day, within the cardiometabolic space, we will show you the overlap of patient populations here from the US. We call it the Venn diagrams.
It's based on the statistics from the U.S. National Health Surveys, and you will basically see the overlap between both diabetes, Type 2, diabetes, of course, obesity, cardiovascular disease, chronic kidney disease, and so on. In each of the sessions today, we will speak to some of this overlap, because that's, of course, relevant for many of the trials that we have done with semaglutide. You see on the right-hand side, where we have completed trials to show what are the benefits for people living with Type 2 diabetes in terms of cardiovascular, benefits. And Martin will show you later more about the FLOW data in the renal space and so on. So it's not only about glycemic control and weight management, but it's even about the broader, you can say, comorbidities, reductions, that we can see with semaglutide.
So just an example, if we look at chronic kidney disease, not in the broader sense, but in a smaller sense, you see here chronic kidney disease, stage 3, that is not exactly the same as what we had in the FLOW trial, but almost, so you can say similar. You will see an overlap of 5 million out of the 35 million patients living with Type 2 diabetes. So there is a significant relevance here for having a molecule that can work on the comorbidities. And in the end, we also know that those are the costly aspects of Type 2 diabetes. When we then look at how much is GLP-1 then utilized, you see here the trajectory over time of GLP-1.
And, you see that today it's only 6% of the scripts in diabetes, that is, or the usage of GLP-1 across the globe. If we look at the U.S., it's 16% of the scripts. If we look at some of the other regions, it is less because we have rolled out later, and so has the competition. But it is fair to say that whenever there's been a new launch into the segment, we've seen an increased usage. But of course, also with the data that we—I just mentioned before, and then Martin will be talking to later, we know that this is, of course, of relevance for using GLP-1 treatment, and especially with the data we have on Ozempic and Rybelsus. When you look at guidelines, they have also changed.
They have now included GLP-1s as first-line usage, and this, of course, means also that there is increased support for physicians to use these products. So overall, it means that with 6% of the scripts today, the potential remains very big in this space, and this is, of course, what we are also embarking on when we are expanding our, you can say, life cycle management of Ozempic with more and more indications, as you have seen the data and will be seeing in the future. So with that potential in mind, I would just like to now hand over to Doug Langa, to hear how we are executing on that in North America. Thank you.
Thank you, Camilla. Thank you, Camilla. It's great to be back at Capital Markets Day. I was reflecting this week that this is my fourth one in this role, and I'll get back to that in a minute. So when we think about diabetes care in North America, you can see that we've had strong performance over the last several years, and we're very proud of that, putting more and more patients on our products. What we saw in the last two years was really a step change in performance, and that came on the backs, as you also see on GLP-1, namely Ozempic and Rybelsus, and I'm gonna get into that in a second. What we also see, and Camilla alluded to, was a category that is still underutilized.
Now, in the U.S., the category grew by 50% last year, and as we indicated, what we saw in the fourth quarter was probably more indicative of what we'll see this year, was in that 30% range. But it still is a growing category that is still underutilized, and we still feel like we have the best brands to produce in that category. So, back to my, capital markets reference. So my first Capital Markets Day was in 2017, and we did it that year in November, for those of you that participated. During that Capital Markets, I had Dave Moore with me, and, and Dave, we had recently hired as, sort of the Chief Marketing Officer.
Part of the hook I had to get Dave to come was this product called semaglutide, and we were hopeful for an approval. A month later, we got it, and two months later, we launched. So if we look back from 2017 to 2023, how did we do? I took some notes this morning in my hotel room, and I was so excited, I didn't want to forget any, so I'll share some of these data points with you and see if you're as excited as me. Last year, we had over 4.5 million patients on Ozempic. 2023, we're a 9x blockbuster, adding... That was DKK 63 billion, adding DKK 24 billion to that, to sales, which equated to a 67% growth YoY.
Even with intense competition, we are still the NBRX and TRX leader. I can say this with confidence, I asked my marketing team again on the latest ATUs, we are the best-known, most preferred diabetes drug in the category today. We're really proud about that. What we're also proud about is that what we still see is 80% of the category is still coming outside of GLP-1. Or if you look again, it's 50% is either naive or generic. We're seeing it used early in their treatment, and we're seeing at least and consistently 80% of that coming outside of GLP-1. What we also see is a stay time of roughly 4 years. Also importantly, we're seeing almost 60% of the patients that start on the product are staying on the product. We feel really good.
We feel really good about the products that we have in a growing category, and we're extremely confident. Now, I would be remiss in not doing my job if I also didn't talk about the opportunity that we've had—that we will have with insulin icodec. We do hope to get a regulatory decision this year. Why we're excited is, I don't have to tell this room, that, in the U.S., we've had challenges with insulin over the last many years. I think we've managed them well. But in my mind, there is no better company, and there is no better place to launch this innovation into a market that desperately needs it. So we have the plans in place, and we're excited about what this product can mean for patients and providers. We also think there is an opportunity.
If you look at the US market, it's about DKK 10 billion in terms of opportunity, and half of that is still with insulin glargine. So there still is an opportunity, and we are really excited about this opportunity and what we can do and what it can deliver for patients. So with that, I'm gonna turn the mic over to my good friend and colleague, my Mike Doustdar.
Thank you, Doug. It's good to see Doug excited.
I am excited.
I can say that, equally, we are also really excited in International Operations . The diabetes business in IO has had a really good, double-digit growth for the last 5-6 years and, and continues to do so. It really, is on a basis of a solid insulin business that we have been building for many, many, many years, and it's quite stable, albeit growing much lower than the GLP-1.
...And then, of course, the more recent years, with the launch of Ozempic in 2019, seeing what Doug just alluded to, a massive growth across various different geographies in IO with the GLP-1 products. If you take that growth area, the GLP-1, and turn them into customers, patients, then you see the part of the slide on your right-hand side. There are around 6 million people in International Operations that use GLP-1 products, ours and our competitors. And that number is around double as much as it was just two years, three years ago. So this is really fast-growing. Yes, 6 million maybe right now is still a small number when you think about the totality of people that need diabetes products, but it's really growing fast.
And you can also see that the money that is generated, the financials that is generated from those 6 million people, 71% of it comes to Novo Nordisk. That's our market share, and it's growing. You see two lines that's growing, that's Ozempic and Rybelsus. Two lines that's declining, that's Victoza and one of our competitors, and then another line that's hardly to see at this point. Just facts. Then I wanna touch upon Rybelsus, because I'm actually quite happy about Rybelsus. In the first year that we launched this product, it's a blockbuster for us in IO, and that we don't see. We actually don't because prices are different, dynamics are different. There are very seldom where you see first year, first launch of any product in International Operations , ex-US, where you see a blockbuster status. We saw that with Rybelsus.
I'm also super excited, of course, about, about that one. Now, when then you think about the dynamic of GLP-1, and I will have one slide on GLP-1 and one on insulin next. The dynamic of the GLP-1 really goes back to, so how many patients are there in International Operation s and, that, that possibly can use some of these products? And Pete, I think you asked a question to Henrik, where he showed you two data points. One, he actually had the number of the products that we had, 40 million, 35 of them are in IO. The other one he did not show you. I have numbers on my slides.
They say the sky is the limit, and honestly, if you take the time into the future, and I don't know how long into the future, that other data point for me internally is that there are 480 million+ individuals that can possibly, at one point or the other, become part of our customers, at one point or the other. And that, of course, super excites us. Actually, when you think about IO, externally, IO is referred to as International Operations . Internally, we think about this as immense opportunity.
When, then, of course, you dig deeper into the numbers in the middle, then you also see, and I think Camilla also a little bit alluded to it, that right now, all the people who are not taking insulin, they're taking actually some of the more modern medications, happens to be GLP-1 and or SGLT2 and DPP4s in a tablet format, then, 4% of the totality. So you see that in the middle. 4% of the totality of the market, diabetes market right now is taking a GLP-1 product. It is a small number, but it's growing so rapidly. And it's growing on a back of, again, number of fantastic products that we have a really strong footprint.
Maybe the single difference in IO between us and our competitor is our footprint on how and where we are with our organization. Ozempic is available today in 78 markets. That's a lot of markets. Rybelsus in 47 markets, and that's actually a competitive advantage that we have, and no wonder why also we have a relatively high share of growth when it comes to both value or volume of these businesses. And again, coming back to Rybelsus here, it says 29% of the value share of growth, 20% of the total diabetes value that is generated in International Operations comes from Rybelsus. That's quite impressive.
Then, of course, insulin, we don't forget that in IO, because as I mentioned, 30 million of the 35 million we serve in IO are still on insulin, and they're very dear to us, so it's absolutely important that we innovate for them, and we continue treating them regardless of where they are across the world. We have still a solid business with our modern and human insulin business. Many people cannot afford some of the products that are coming to the market right now, but we have actually fantastic drugs for them in human and modern insulin, and we'll continue to serve them. Next-generation insulin also gives us many patients around the world.
We continue serving them, but of course, before I leave, I have to say I'm super excited that we're getting very, very close to the launches of our two next insulin products, icodec and IcoSema. They're going to be fantastic, predominantly also because the segment they serve, the basal segment, is the largest where we don't have yet leadership. So market share gain in that segment with the weekly best-in-class product excites me immensely. And then hopefully, soon after that, many more things, and who better to say that than Martin?
Thank you very much, Mike. So you've already heard it a couple of times, we work in areas and in disease areas where there's a huge unmet need. We still see that in Type 1 diabetes, we still see that in Type 2 diabetes, and that basically means that we will continue to innovate in those disease areas. We have a strong pipeline. Looking at what we're doing currently in both the subcutaneous, but also the oral, incretin space, we have a leading pipeline. Obviously, building on semaglutide, where we're now not only focusing on glycemic control, on weight loss, and weight loss is also incredibly important in Type 2 diabetes, but we are also focusing on comorbidities. We know for a couple of years that Ozempic is associated with a 26% decrease in risk of cardiovascular disease.
We've just released the FLOW data, and we'll continue to look at other aspects of comorbidities related to diabetes. But we'll also do innovation, and it's very, very clear that combining the base of GLP-1, specifically semaglutide, where we've seen these amazing outcomes, with novel biologies, is leading to next generation of innovation. You've seen the amycretin data from Marcus this morning. I don't think it's a secret that we in this company like the amylin biology. Amylin is boding incredibly well in the obesity space. We'll come back to that, but actually also in the diabetes space. And having two assets, one in phase III and one in phase I, already at this point, is a really, really strong proposition.
In particular, when we combine them with Henrik and his ability to scale, we believe that we can have a truly differentiated and very, very competitive pipeline in this space. We also have to say there's still room for innovation in the insulin space. You've heard Camilla, Doug, and Mike talk about icodec. We have very high aspirations for icodec. It is an incredible innovation in terms of efficacy, combined with good safety, and at the same time, it's more convenient than ever for the patients. I can say the same thing for IcoSema, and therefore, we are very, very proud of the continuous innovation that we'll bring to our patients. And Marcus and his team are working hard on also getting our glucose-sensitive insulin back into phase, into human testing. But we also have a keen eye on Type 1 diabetes.
You've heard it also from Marcus, one of our focus areas is to change the trajectory of disease, either preventing or maybe even curing disease. We have that outlook in Type 1 diabetes, both actually the prevention part, but also the potential for curing part through cell-based therapies. Obviously, incredibly exciting. I'll do a few deep dives now, starting actually with what we're doing with semaglutide, the FLOW trial. If you remember from Camilla's Venn diagram, there's a big overlap between Type 2 diabetes and kidney disease. A big number of patients suffer from chronic kidney disease if they have Type 2 diabetes. This leads to detrimental outcomes, both kidney-related, but actually also cardiovascular-related outcomes. And we have to remember, both in chronic kidney disease, but actually also in liver disease, the biggest reason for premature mortality in this space is actually cardiovascular mortality.
The FLOW trial was designed in an outcomes manner, where we looked at semaglutide 1.0 mg versus placebo, and the primary endpoint was a 5 composite endpoint, looking at time to first event in either kidney-related or cardiovascularly related endpoints. We are really, really happy about the data. The primary endpoint that evaluated 5 components, 3 related to progression of chronic kidney disease, 2 to the either risk of kidney mortality or cardiovascular mortality, and combining those 5 endpoints, we saw a 24% decrease in risk. I think it's important to call out that this is on top of standard of care. At the end of trial, more than 30% of patients were actually on an SGLT2, and still, we see an amazing 24% decrease in risk.
I think it's also important to call out that both the CKD and cardiovascular components contributed to the primary endpoint. I may wanna call out. I can't give you the number, because we still have to publish it, but I do wanna call out that if we, for example, look at cardiovascular disease, we see a significant decrease in this population, specifically for cardiovascular disease. That's actually quite amazing. I don't think we've ever seen that before, and we take a lot of pride in what semaglutide can do in this space. It doesn't really stop there, because if we allow ourselves to just spend a little bit of time on the secondary endpoints, the confirmatory secondary endpoints, these are actually quite amazing. Obviously, we have a very nice hit, 24% risk decrease on the primary endpoint. That's a composite endpoint.
But we also look at the change in GFR, that's glomerular filtration rate, and that's a measure of kidney function. And what we can see is that semaglutide changes the slope, delaying the progression towards end-stage renal disease... Importantly, and that's the third confirmatory endpoint, semaglutide significantly reduces the risk of having a major adverse cardiovascular events. That's stroke, that's myocardial infarction, and that's cardiovascular death. And finally, we also see that semaglutide decreases the risk for all-cause mortality. All of this is statistically significant, and obviously, in this trial, clinically exceedingly relevant. I just want to remind you, it's the second time in a matter of a couple of months where we show that semaglutide decreases all-cause mortality, in diabetes, but also in obesity. So really, really strong offering, and very excited about the data. We continue that journey.
A lot of patients who suffer from both diabetes, but actually also obesity, suffer also from what we call osteoarthritis. That's not what I'm gonna talk about here. I'm gonna talk about atherosclerosis. So I apologize for that. A big unmet need also in this space is obviously the part of cardiovascular disease that is peripheral arterial disease. More than 200 million patients suffer from this globally. It is closely associated with atherosclerosis. We've seen in our previous trials that semaglutide can actually reduce, and these are retrospective analysis, can reduce the risk of having peripheral artery disease. It's big, and there's a huge unmet need because there's no treatment available. 25% of all cardiovascular disease has the nature of peripheral artery disease. This is debilitating for the patient.
They can have less functionality, and therefore, if we can change that outlook, obviously, we need to do that. STRIDE will read out during the first half of this year. We're looking very much forward to that. It's again a simple trial. Patients randomized to either semaglutide 1.0 mg or placebo for 52-week, 52 weeks, looking both at the primary, but also secondary endpoints of functionality, improving functionality in these patients, but actually also looking at the harder endpoints of what we can do in this space. I wanna go back to my secret love, and that is amylin. Maybe it's not so secret anymore. You've seen these data before. This is what makes us excited.
In a reasonably small Type 2, phase II, program in Type 2 diabetes, we see that amylin, combined with semaglutide, improves glycemic control significantly and clinically relevant 0.4 percentage points after 32 weeks. We also know from amylin biology that that improves over time, so we do actually have a potential for aspiring for even better glycemic control when we do a more than a year-long study. But what is even more exciting is the weight loss that we see in Type 2 diabetes. Currently out there, you see weight losses around 13% at the max in Type 2 diabetes. Based on these data, we can safely say that CagriSema holds the potential of delivering maybe more than 20% of weight loss in Type 2 diabetes. Clearly differentiated, and this is why we love it. We also see more than additivity.
We actually see synergy on cardiovascular markers of risk. So we are taking semaglutide into phase II in diabetes. We still haven't seen... amycretin. CagriSema is currently in phase III, so, so, this is obviously something that we are very excited about. We will see readouts of that next year. But going back to Marcus's point, we are also excited about what can amycretin do, not only in obesity, but also potentially in diabetes. We haven't seen diabetes data for amycretin yet, and that basically mean that we are now conducting a phase II trial, and you are asking me how long that will take.
I will just point you back to the CagriSema days, where we also did a phase II trial for Type 2 diabetes, and we did that, I think, faster than I've ever seen a phase II trial being conducted before, and we intend to do the same thing for amycretin. It doesn't really stop here. We also actually have some really, really nice data for our GLP-1 GIP. You saw from Marcus that we're working both on a once weekly, but potentially also on a once monthly. That holds big potential also. We see some very strong data on glycemic control, some very strong data on weight loss. Maybe not fully to the tune of what we see with CagriSema and a mycretin, but still very exciting.
We're very excited about what we see in our pipeline, both in the clinical space, but certainly also what is coming in from Marcus in terms of novel biology. We believe that is required, because the number of patients who suffer from both Type 1 and Type 2 diabetes is increasing. There's still room for innovation, because there's still a huge unmet need. We believe that part of that need can be addressed by incretins, maybe combined also with the amylin biology. Given that around 6% of patients globally today are on a GLP-1 analog with Type 2 diabetes, there's a big growth potential.... but there's also a big potential for innovation, and obviously, we are very proud and happy with what we do with icodec, IcoSema, CagriSema, and amycretin.
With that, I think we will invite both the presenters, but also Lars to moderate our Q&A.
Thank you, Martin. And let's get our colleagues up. And obviously, it was easier in the old days when there was only one molecule in development, so now we have to keep track of all of them.
Even I get confused.
So maybe we start from this side this time. Yeah. Yeah.
Thank you. Peter Welford, Jefferies. I wanted to ask you a question on what excites you the most, amylin. Curious in particular, actually, it was the presentation before, you talked about a new amylin in the pipeline. Curious, what is it you see that potentially could be bettered on cagrilintide? And, you know, what is the rationale therefore for pursuing, in your mind, a better or newer amylin?
So we know already from the GLP-1 space, that you can always improve the your approach to the biology. We've seen that going from Victoza to semaglutide, and obviously, we want to pursue the best possible amylin monotherapy. At this point in time, it's exploratory. We're really, really happy with what we've seen, obviously, with cagrilintide, but we are specifically also very happy with what we've seen with the monocomponent, the unimolecular format of amycretin. So currently, we are adding to our pipeline, but it also allows us to choose, because as both Marcus and I have spoken to, we'll not bring not differentiated products to the market. We don't think that's who we are, and that's not helping patients.
So obviously, allowing ourselves the flexibility of choosing is an important part of what we do when we double down in both diabetes and in obesity.
Thank you. Here.
Thank you. It's Harry Sephton from UBS. On the FLOW data, can you talk about the SGLT2 use? Can you specifically show an additive effect over SGLT2 with Sema in this study? Is that a subgroup that you're gonna look at specifically?
So these are early days. At the baseline of the trial, we saw 15% of patients being on a SGLT2. More were added in during the course of the trial. At the end of trial, approximately 30% were on an SGLT2, and actually more on placebo than in the semaglutide arm. And this is probably to be expected. What we also see is actually that the number of events, because it is the smaller population, is lower when we combine GLP-1 and SGLT2. And therefore, we should be a little bit cautious to interpret the data.
I think it's very, very clear, specifically on the cardiovascular endpoints, that we see that the benefit of combination, or rather the benefit of semaglutide, is there on top of SGLT2.
Martin?
Thank you. Martin Parkhøi from SEB. Just, to Martin, maybe you could elaborate a little bit, because we saw you highlighted that we see a superiority on all-cause death. But comparing to SUSTAIN 6, which of course also was in diabetic patients, that was actually it's what's actually 1.05, as we call it, on the hazard ratio. So what's the difference between these two trials that you can end up with two different results?
So, you've heard me say this a lot, a good number of times. I'm really concerned, always, comparing across trials. I've also heard some comparisons to SGLT2 trials and their outcomes. There are differences in population, so duration of diabetes, how many patients have, and in SUSTAIN 6, not all patients had chronic kidney disease. Only around 40% of patients had chronic kidney disease. Here, obviously, all patients had chronic kidney disease. There's a difference in the level of cardiovascular disease. In FLOW, these patients were very, very sick with established both heart failure, previous MI, previous stroke, established peripheral artery disease.
There's a difference in the background medication, and we actually see that the FLOW trial has a very high level of RAS blockers, a very high level of hypertension, very high level of dyslipidemia, all of those to the tune of 90%+. And that basically means that you can't really compare neither to SUSTAIN 6, where the actual endpoint also was different. So the composite endpoint that we have in FLOW is different, what the endpoint described as SUSTAIN 6's. Can't really compare across. If you really wanna know, you have to do the head-to-head.
Thank you, Martin. Richard?
Thanks. Richard Vosser from J.P. Morgan. Maybe just going back to the, GLP-1, GIP. I mean, you've talked about amylin very passionately, but you're doing a monthly version of GIP, GLP-1. You know, what's different, I suppose, in the biology that doesn't allow you to do a monthly, or should we expect that for amylin? And sort of, you know, why pursue GIP? You've talked about cardiovascular may be not as good, so just why even pursue it?
So, GLP-1 GIP is not bad. We believe that from a weight loss, from a glycemic control, but potentially also from a cardiovascular perspective, amylin plus GLP-1 is better. But we do see, and you saw that in the slide, we do see good weight loss, and we do see good glycemic control with GLP-1 GIP. When Marcus then has the opportunity to investigate a less frequent dosing, in this case, once monthly, in that biology, then obviously we take that opportunity because it's not a bad biology. We just believe that GLP-1 amylin has a bigger potential.
Michael, and then we move backwards.
Thank you. Michael Novod from Nordea. So Martin, can you say in five years from now, where do you stand in terms of generational-wise on the SNAC technology and the ability to significantly increase bioavailability? In that respect also, is there a way for this technology to reduce the food and water restrictions?
So specifically, on water restrictions or fluid restrictions, we don't see a big impact on that, neither in our clinical trials nor in the market. I think Mike spoke to the success of Rybelsus, so that's really not a big concern for us. Obviously, we're looking into this, but it's not our biggest focus area. On the generation and the bioavailability, we see continuous progress. You've already seen us moving into the next generations. I think Marcus is currently working on generation seven. Not all of those will be taken into the clinical space because obviously, again, it has to be not a minimal, but rather larger stepwise improvements in what we see in terms of bioavailability.
We see that continuously, thereby also supporting Henrik in his endeavors.
Simon?
Thank you. Simon Baker from Redburn Atlantic. I'll give Martin a breather on this one.
Thank you.
This question is essentially for everybody else. Tying back to what you said in the presentation this morning, Lars, that we, we've seen a lot of data today and previously showing tremendous growth of GLP-1, whether it's in diabetes or obesity, but still very low penetration in the grand scheme of things. So I was wondering, as you've demonstrated more on the benefit of GLP-1 across both indications, how has the cost-benefit discussion with payers evolved? Because I'm assuming it's getting incrementally a little bit easier as they see the benefit. We're still at a very low point. How has it, across different regions, changed? Do people get it more than they used to a few years ago, and how should we then think about where we're headed in light of that? Thank you.
Thank you, Simon. So maybe Doug and Mike, a perspective on how you see, say, the payer action, and maybe while you think about that, Camilla, you can allude a bit to the overall health economics.
Yeah
... perspective we see for this type of medicine.
Yeah, so as a starting point, you know, we're still at over 95% access for both Rybelsus and Ozempic, so that's extremely positive. And I would say part of our job is always to demonstrate the value of our brands, and yes, to your point, as we see increase in indications and the potential penetration benefit into other comorbidities, I don't know if the conversation is getting easier because the flip side of that is that the size and scale is getting larger. But certainly, those are more robust conversations as we're having them with vertically integrated health systems. So yeah, I think it's a benefit for us, the amount of data.
I think on the penetration question, you have to separate the generation one and generation two of GLP-1. If you think about the generation two, Camilla showed a picture that penetration is around 15% in U.S., where we went first, and lower because simply this has been just a few years, not mentioning COVID was in the middle of the whole thing as well. Having said this, within diabetes, across the world, GLP-1, to a large extent, is reimbursed right now, so people have understood the benefits of products like Ozempic and Rybelsus. It's our job now to bridge that into the obesity, of course, and make sure that that continues.
Yeah. On that point, in the health economic models, in the beginning or a few years back, we saw mainly a focus on HbA1c and then a modeling in terms of what would that mean in terms of risk of other serious complications. But now we actually have the exact data, so we don't need to rely on DCCT, if some of you remember that, and UKPDS more than 20 years ago, even 30 years ago, soon. So we actually have that data now, and that goes into these models and the discussions. To Doug's point, cost effectiveness remains very important, but of course, budgetary impact short-term is equally also an issue.
But of course, here some of the data that we also generate. We can also show impact on hospitalization and other things that are sometimes quite immediate even.
Good. That perfectly closes the Q&A session on diabetes, so we now have a slightly shorter break, so 10 minutes. Please be back after a short break. Thank you very much.
My weight was 140 kilos as a teenager. I was always the person no one want to have on their team because I'm fat and I'm bad at sports. It's tough for me to think back on the time. I think about the kids today, and I just hope that they will never experience the pain and the suffering that I did. I want to make a change. I joined a patient organization, and I have some online conversations - Hey, Sam ... - with people living with obesity. It's a safe place, so they can talk. I want to give back. We must stop fat shaming, and I want Novo Nordisk to be part of this change.
... Even today, we see misconceptions, we see stigma around, around obesity. We are also a little bit happy to say that spearheaded by Wegovy, supported by SELECT, the dialogue of: is obesity a disease? Does it need to be treated? Is changing. I think that's supported by numbers. We know obviously obesity is increasing, and that is globally. A lot of countries are trying to catch up to the U.S. in a bad way, and, when I, in the slide, show that, that we're expected to exceed 1 billion by 2030, actually, numbers are coming out suggesting that we are getting there already this year. So it's big, and we also know that obesity is associated with a great number of comorbidities in the metabolic space, in the cardiovascular space, but also in the mechanic space, so to speak.
Life expectancy, if you suffer from obesity, is substantially and fundamentally decreased. This is exemplified on the right hand of the slide. If you are age 46 today, likelihood, if you have normal BMI of reaching age 70, is 80%. If you just have BMI between 35 and 40, it's down to 60%, and if you exceed 40 in BMI, it's down to 50%. This is a serious chronic disease in need of intervention. The overlap between obesity, and I think from a pathophysiological perspective, if you really try to simplify it, obesity is the starting point. That basically mean there's a huge overlap between obesity and diabetes, but also obesity and cardiovascular disease, obesity in this space also heart failure with preserved ejection fraction. But we'll later in the day also show other comorbidities, including chronic renal disease and kidney disease.
Our focus has and will be on weight loss. That's the fundamental of first intervention of obesity. We started out with Saxenda, then we went on to 17% weight loss with semaglutide, and obviously we've already a little bit discussed what we believe the amylin biology can do, starting out with cagrilintide. But on the other side of the slide, the outcomes become incredibly important for the individual patient, for payers, for regulators, and for broader society. If we boil it down and include the comorbidities, obesity is one of the most expensive diseases that we have in society today. That's why we like SELECT. A lot of you have talked about the primary endpoint of SELECT. We saw a 20% decrease in risk of myocardial infarction, stroke, or cardiovascular death. We can talk a lot about that, and there were some questions on number needed to treat.
I think just looking at the primary endpoint is honestly too simplistic, because we also in SELECT saw a decrease in cardiovascular death, albeit not statistically significant, a substantial decrease in heart failure, almost 20%, an almost 20% decrease in risk of all-cause mortality, and more than 20% reduction in kidney risk. It basically means that we can assume kidney benefits for not only patients with diabetes, but also for patients with obesity, and a 73% reduction in diabetes. It doesn't really stop there. In SELECT, we also looked at more comorbidities, but these are maybe some of the big-ticket items also from a health economic perspective. In a post-hoc analysis, if I allow myself to pool this, we can actually show a 37% risk reduction being on semaglutide versus placebo.
If you wanna translate that into number needed to treat, after the first year, number needed to treat is 45 people on the primary endpoint alone. Sorry, 45 people after 4 years. But if I look at the composite endpoint, after the first year, it's 20 people. If I look at 4 years, which is what constitute a chronic disease, it's 9 people. These are staggering numbers. We can make a true impact for patients living with obesity, with a really, really great intervention. It's no doubt that SELECT is an incredibly strong tool. We also received a question on that in the previous section. But we've seen this in more than one trial. I've talked about the STEP-HFpEF trials a couple of times.
I'm again, not allowed to show you the actual data from just the STEP-HFrEF trials, because we are still aiming to publish those in a prestigious journal. But if I allow myself to just show you the pool of STEP-HFrEF/HFpEF ... and SELECT. STEP-HFpEF are really a very well-defined population. In SELECT, we pool heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. But in STEP-HFpEF, we only look at heart failure with preserved ejection fraction. But if I allow myself to pool the data, we show that we can reduce the hospitalization, very expensive hospitalization for heart failure, with 58%. If I look also at cardiovascular mortality, we look at a 39% reduction.
This is a really, really strong data, and those of you who go into the numbers can probably imagine what we will actually see coming out from the individual STEP-HF trials. This is why I'm doing drug development. You saw Isabelle this morning. She had heart failure. More specifically, she had heart failure with preserved ejection fraction. That's a disease that is closely associated with obesity, and she described what being on this drug meant for her in terms of her everyday life. But we can now also tell her that we can reduce her risk of going to hospital and reduce her risk of premature death. This is why we do business. And to talk about how we do this in the commercial space, I'm super happy to invite Camilla to the stage.
Thank you, Martin. Thank you. Yeah, thanks a lot, Martin. And there, there is no doubt that with Wegovy and the data that we have provided from clinical development and research, we have been able to truly unlock the diabetes market. And we have also been able to reach our strategic aspiration, as Lars mentioned this morning, and this will not stop us from progressing further. As you see now, Wegovy and Saxenda together is 18% of our total sales, and at the same time, of course, we are also looking at what is the total unexploited potential. You see here, and Martin talked to it, the more than 800 million people living with obesity, and we are treating around 1 million.
So there has been a number of changes that we have been working on before the launch of Wegovy, but that we've also seen materializing after the launch of Wegovy. I'd just like to take you through sort of three elements of that. With regards to patients, before the launch of Wegovy, we saw that patients were in doubt. "Is there help to get? Should I just exercise more and eat less? Is that all I can do?" They were used to that message from physicians. But now we know that the obesity market is driven by people showing up at the physician's office, and a big, big part of the prescriptions are driven by patients asking for more help. So that is a significant change. We also saw before that the stay time and adherence was relatively low with Saxenda.
But we see now, because of expectations to longer weight management and because, of course, also, affordability, access, and also about, the efficacy in itself, that there will be a longer and longer stay time, and we see very significant and very good improvements in that. At the same time, with prescribers, it's not long ago that not every physician was, reflecting on whether to prescribe obesity products or not. They mainly would not be doing that. But since we, after the launch of Wegovy, just in 3-4 years, we've seen that the number of physicians prescribing are up fivefold, approximately. So just to say that more and more physicians are now truly considering prescribing obesity medication, and the guidelines are also still improving, yet of course, that takes a little longer time.
When it comes to payers, Doug and Mike will be talking to this in a minute, about how, of course, also access has significantly improved, in many parts of the world, not only with Wegovy, but we've even seen it accelerate also with Saxenda in recent years. So the understanding of why to treat obesity is much greater than what it was just a few years back. As I said, this should not stop us and think that we will be able to solve all problems in terms of potential. We are going to continue to expand our pipeline. We now have the only molecule that has cardiovascular proven benefits in Wegovy. We are looking at pipeline innovations, of course, also, that Martin will be talking to a little bit later, both in the injectable but also in the oral space.
Then, in addition to having a great pipeline and great innovations, great efficacy, great convenience for patients, what is equally important, due to the size of the numbers in the obesity space, is the ability to scale, the ability to bring this product to many, many, many patients. You heard from Henrik this morning how we are planning to be able to do that. And that in itself is, of course, in this space, with such a big potential, a strong competitive advantage. We are also aware of the fact that some people, they're living with obesity, are not able to pay for some of the innovations. So when we are rolling out Wegovy, and when we are reflecting on how we can support them best, we also have allocated volumes to the most vulnerable patients.
Of course, we're also looking to seek reimbursement in more and more countries, not for everyone, but for parts of the populations and segments where we have a good dialogue with payers on the cost effectiveness, as we spoke to earlier. And then we are adjusting our commercial model to also reflect on: How can we better support patients when this is now a pull market, a patient-driven demand that is out there? And this, of course, also has to do with online opportunities and other ways to support patients.
And then finally, before I hand over to Doug, just wanted to share with you that we know from SELECT that the cost-effectiveness of treating with semaglutide 2.4 compared to our Saxenda population and the STEP 1 population is significantly better and up to twice as effective. And we also see that when we then look at sub-populations from this, from the SELECT trial, we see that the cost-effectiveness is even stronger than that. So of course, when we are looking to having these discussions with payers and policymakers, then it is very important data to have.
And as you see on the bottom here, we talked about it earlier in the diabetes section, the questions around cost-effectiveness now do not only look at weight loss and surrogate endpoints, but truly look at some of the events that we have very clear and significant data on. So, CV events, fatal events, hospitalization, and so on, and the sustained weight loss. So all of that means that we have a great starting point for having discussions with payers on the SELECT population, of course. And so with that, I'd like to hand over again to Doug, to explain a little bit about how we are doing this in the U.S.
Thank you, Camilla, again. So maybe as a starting point, I’d tell you that in over 30 years in the life science industry, although challenging, this is the most, I’d say, exciting and rewarding disease state that I’ve ever participated in. And I say that whether it’s coming from family members that are impacted or the concern I have actually for my own country, as Martin alluded to, with our population growing to, in the next couple of years, could be almost 50% of the population that is clinically obese. It’s a health crisis that needs intervention, and we have a product that can help. It’s called Wegovy. So how did that product do in the U.S.? So even with supply constraints last year, Wegovy performed extraordinarily well. You could argue it was one of the best launches that we’ve ever had in the U.S.
It's the second-largest contributor to growth. As you can see, it added DKK 23 billion, and we're very pleased with the performance. What I was also happy to indicate on the full year earnings was that we started releasing more product into the market of the starting doses. As you all know, something that was critically important to us last year was continuity of care. So to make sure that patients that started on Wegovy could stay on Wegovy. So we reduced the starting doses into the market, so we're very happy to re-release them in early February. In the first couple of months of February, we've seen an impact already at NBRX, and we're excited about that. But it is about patients.
Whether we heard from Isabelle, or two years ago, if you remember, Lars interviewed a patient called Lisa, who participated in our clinical trials. And although they always reference weight, some of the things they also talk about are the simple things in life: climbing up to the top of the stairs. Lisa talked about playing tennis again, going for a walk, things that many of us may take for granted. So for us, the narrative is moving away from just absolute weight into more health and life. And we feel confident, and you've heard this all morning, about the heart outcomes data that we're gonna see or are seeing in SELECT, that we have the product that can talk about that, that can no...
It could, it could not only help the patients, but it can be a competitive advantage for us. So excited to get that out. Now, these are the characteristics of what we see in patients today, and what I'll have you zoom in on is the comorbidities. Again, maybe another proof source here, which is, if you look at the Wegovy patients today, again, it's skewing toward female. You can see the average age, the BMI, but over half the patients have two or more comorbidities, and a third have three or more. So we know we have to take this discussion beyond just absolute weight, and that's what we're doing. What we also see, and I know we get a lot of questions, so maybe I'll just address it now and save time.
Because of the supply constraints that we've had, it's very hard to get to an exact number. But what I can tell you is that Saxenda is at 4-5 months, Wegovy is greater than 6 months, so it's directionally in a good place, and we believe that will get better over time. But we also see, importantly, that over 30% of the patients are staying on the product for over a year. Now, some of the 3 pillars that I've talked to you about over the years have been activating patients, and Camilla alluded to that. We see more patients being activated. It's market access and reimbursement, and it's also prescribers. We just simply, over the years, we've needed more prescribers. So last year, we more than doubled our footprint in the U.S. and, in essence, doubled our call plan.
And you can see, if you go back to 2022, we had about 90,000 prescribers, and then 2023 is 179,000. So we are making progress. Now, you hear pull market a lot, and, and as evidenced by the middle of this, we do see that the prescriptions coming from, in essence, non-called on, are greater than what we see in called on. So the good news is, more patients like Lisa and Isabelle are getting the courage to go speak to their physicians about weight and what they can do about it. So that's good. But what we also know and what we see from the data is that we're seeing twice as many prescriptions come from the called-on doctors.
So what that tells us is, is that dialogue that we're having around education and all the components within that are still very important. So market development and education is important. That's why we had field sales teams, medical educators, medical liaisons, and market access teams, et cetera, which we will continue to deploy. What we also do is we don't leave the non-called-on universe alone. We have a lot of information that we give, both that's intended for consumers and HCPs, and we will continue those efforts. One of them is Rethink Obesity. It's a non-branded campaign for awareness for HCPs. I'm happy that recently we hired a, I'd say a top executive last year from a competitive life science company, to come in and continue to transform marketing.
So these programs and services will continue in our, in our, called on and our non-called on universes, and we're proud of the efforts that we're making there. Lastly is market access, something that is near and dear. We are pleased, and we've said this over time, with the 50 million patients that we currently have access to Wegovy today. What that correlates to, as you can see, is 80% of the patients are paying $25 or less. So it's working. Are we satisfied? No. We're gonna continue these efforts. As you can see, we're gonna have some opt-outs. Unfortunately, that does happen, and that's not good for patients.
But we're seeing a lot more opt-ins, and so the net effect is we're adding more lives YoY, and they are coming in various federal channels as well as states, and certainly commercial market. And lastly, what I would say is that we do believe that, that with SELECT, this does add to the body of evidence that we have. That body of evidence we use all the time, to the question I just got earlier. We are gonna use it with Medicare. I'm not saying that, that Medicare is gonna reimburse overnight. There may be an opportunity through CVS, but it does add to the body of evidence, so we're very pleased that we have it, and we're gonna continue to make sure that market access is front and center. With that, I'm going to turn it over to Mike.
Thank you very much. Doug, Doug's numbers are so good, he starts stuttering. I hadn't seen that before. I actually, in that context, as he was showing his numbers, I was a little bit trying to think, how can I excite you with my numbers? He showed DKK 29 billion worth of Wegovy sales, and I have DKK 2 billion only. And then I thought the way actually to look at this slide, it's almost a copy and paste of Doug's slides on the left-hand side. The way to look at this is that although the bars are much smaller in number and the colors are reversed, look at it in the context again of IO and maybe Saxenda. Saxenda was launched in 2015 in IO, and we have it in 76 markets.
In 2021, we did DKK 3 billion with that. Wegovy in the first year, launched with capped volumes in less than a handful, did DKK 2 billion. So as we get going with Wegovy, as the supply will come, as the launches will be released from their caps, this is gonna get big. It's gonna get very, very big. Where we have actually Wegovy now are the eight flags you see, the eight markets where we have launched them. They are very special launches. We, we don't have a big launch event like usual. We, we don't go to all the different targeted doctors.
We segment which doctor, which institute, which hospital, should be prescribing the medications, and we really make sure that the right people get the product first and foremost, as we launch and go forward with this. I could not bring all the examples of all the markets. There's not enough time. But I thought that actually, in order to give you a bit of a contrast to the U.S. picture that Doug showed, I take this market, Denmark, and give you a bit of an insight on how the product is available in Denmark. Then you could see on one side of the slide, of course, the TRXs per month, that you can take a look. But the 7%, I think, is quite important to look. 7% of the obese population in Denmark right now is on Wegovy.
Or you can make the calculation differently. If you take the total population of Denmark, 1.5% of Denmark is on Wegovy. We have never seen a product like that, ever. Then on the other side, their number is very similar to Doug's, a little bit up and down. The 71% female is a little bit less than what Doug showed. The 36 BMI, I think Doug showed 38. Very, very similar. 8% comorbidity is also very similar. The difference is on the last part of the slide, fully out-of-pocket payments. Wegovy right now is out of pocket in International Operations , 7 or 8 markets that we have launched. People are willing to pay for it. So there is, of course, a lot of pressure on the healthcare professionals, on the GPs that have to prescribe these products.
And then there is this other thing that says "inequality in health," where we really need to pay attention to as we expand in IO. Inequality in health, because even if you take Denmark, a highly developed, high GDP per capita country, and look at the prescriptions, then you see some differences. A lot of the prescriptions are coming from North Zealand, where the more affluent people are living. So as we go much, much broader into emerging markets with this, we have to really make sure that we don't leave anyone behind, and we cover everyone. And one way to do that is to really make sure, besides, of course, acknowledging that out-of-pocket will play a very big role in this type of a product for a long, long time, we need to double down on reimbursement. With Rybelsus...
Oh, sorry, with Saxenda, we actually did pretty well. 20% of the population that was getting Saxenda in IO was reimbursed. 80% was out of pocket. Early signs with Wegovy are also good. We have made a good forward leap in our dialogues and discussions with the government of UK. Actually, last week, Switzerland reimbursed the product, and we're in good dialogues with the other countries as well, and we will do so as we launch into more and more places. And of course, what will help reimbursement is data. SELECT is fantastic starting point to have the discussion with the various different people, and more data and more pipeline will excite all of us, and who better to talk about that than Martin?
Thank you very much, Mike. Obviously, we can't talk obesity without also talking about the clinical pipeline. You heard about our philosophy on doing research, development, approaching obesity from Marcus. Obviously, we have to look at the weight loss. We have to look at the comorbidities. We have to look at the healthy weight loss, ensuring that we are preserving the right proportion of lean body mass. We have to look at maintenance, and then, obviously, we have to discuss safety and tolerability. I just wanna make one comment that I didn't make before on, on, SELECT. The amount of safety data that we have on the semaglutide molecule from diabetes and obesity at this point in time is second to none, and every time we do a major placebo-controlled outcomes trial, we confirm the safety profile of semaglutide.
That is, in and of itself, an incredible differentiator. Obviously, we aim to continue that journey, having a very high focus on safety and tolerability of our anti-obesity medication. Marcus also talked to the dosing frequency, and we'll discuss that more also at later meetings. We are really, really happy with having a broad, deep, and differentiated pipeline. I'm gonna come back to discuss my love for the amylin biology also in this space. But just on this slide, I may wanna point out, first of all, that we expect regulatory approval in U.S., but also in Europe, for the SELECT label update that we submitted during second half of last year. And that will happen in a not so distant future. I also wanna point out the 7.2 mg that will read out in second half of this year.
Our models tell us that without compromising on safety and tolerability, we can actually expect around 20%-21% weight loss with 7.2 mg of semaglutide in the obesity space. So a step up in and of itself. Not to the level of CagriSema or amycretin, but still a step up. Now, I get to talk about osteoarthritis. Osteoarthritis is a debilitating condition in obesity. A lot of people, and we've talked about that, live with a cardiovascular risk, with a renal risk, with a liver risk. We heard from Isabelle that having heart failure with preserved ejection fraction impairs her functionality. A big proportion of patients living with obesity also have impaired functionality due to osteoarthritis. We conducted STEP 9.
It is an exploratory study, so a reasonably small study, 400 patients, where we compared semaglutide 2.4 mg to placebo, and investigated in a co-primary endpoint, obviously the weight loss, but then the functionality and pain associated with osteoarthritis. We are really, really happy with what we see, because in this small study, we actually show not only a statistically significant, but a clinically very relevant decrease in what is called the WOMAC score, between friends, assessing functionality and pain in these patients. Again, taking the holistic approach to obesity, just as we did in diabetes, we actually can serve the patients in the best way.
And we've already talked about the results coming out of the SELECT trial, the STEP HF trials, and combining that with the STEP 9 trial, we continue to add to the evidence pool that we have for semaglutide. My next love is obviously CagriSema. You've seen the data a couple of times in obesity. We know that it holds great potential, at least 25% weight loss, with a safety and tolerability profile that in phase I, II, was similar to that of Wegovy. So we get more bang for the buck, so to speak, without having to compromise on safety and tolerability. If we can show that in phase III, that's really gonna be a game changer. We also discussed the potential, obviously, on the cardiovascular system.
We've seen more than additivity on some of the biomarkers for cardiovascular risk, blood pressure, dyslipidemia, but actually also inflammation. That holds big, big potential for what CagriSema can do. We'll see the first readout from REDEFINE 1 later this year, and as you can also see in the slide, late this year. That's gonna be incredibly exciting. That's our pivotal study. It's a 68-week study in 3,400 patients. And if I can use a proxy for future success of a molecule, it's typically... How easy is it to recruit into a trial? We actually recruited these 3,400 patients several months prior to our schedule, and that obviously, again, at least in my mind, and it is a proxy, speaks to the potential of CagriSema. These patients and these physicians appear to like CagriSema.
REDEFINE 2 is a Type 2 diabetes study. As we've already discussed, big overlap between diabetes and obesity. Good number of patients, almost 80% of patients with Type 2 diabetes, have obesity, and establishing weight loss in that population is incredibly important. And as we discussed in the previous session, CagriSema appears to, in Type 2 diabetes, introduce a weight loss that is second to none. So again, a key differentiator. I've talked about the cardiovascular potential of CagriSema. We're investigating that in REDEFINE 3. REDEFINE 3 is a hybrid trial in the sense that we've been allowed to, investigate patients with obesity, as well as patients with diabetes and obesity. So REDEFINE 3 serves not only for the obesity program, but actually also for the diabetes program. And then obviously, a lot of you have put attention on REDEFINE 4, which is a head-to-head against tirzepatide.
We do a similar study in the diabetes space. And again, based on what we see so far, we're really, really confident that CagriSema will show some very, very convincing data. The potential of CagriSema also warrants us to take this maybe even further. Obviously, we'll investigate obstructive sleep apnea, but we'll also specifically go into heart failure, chronic kidney disease, non-alcoholic, but also alcoholic liver disease. So additional aspirations in the diabetes space. Again, we have really, really high aspirations and high confidence in this biology. But it doesn't stop here. These days, we do both internal and external innovation. Monlunabant, or INV-202, is an externally acquired asset. As Marcus alluded to, there's even a follow-on, INV-347, but right now, we are currently investigating monlunabant in clinical trials.
These are actually published data, and we can always discuss how convincing is a placebo-controlled 4% weight loss. You have to consider this is after 28 days. So we, when we put that into our model, we expect around 15% weight loss, and that is in a tablet form. And if we, to Marcus's point, can rule out new psychiatric disorders, it also appears to be very safe and tolerable. Really, really big upside. When we then also combine that with Henrik's ability to scale, because we think about that, and we believe that we have a competitive edge there, this is a very, very strong offering. You've already seen this data. At the very least, amycretin has the potential of showing same efficacy and safety as CagriSema, and we have the ability to bring that to the patients in either an oral or subcutaneous format.
We're currently investigating the subcutaneous format in phase I. That will read out sometime in 2025. And then we'll look at the data, and we will figure out how to go into what I would call an ambitious further development program. This is high potential, and it is something that we will investigate in a very diligent manner. I've been asked a couple of times if we will skip phase II. I will not rule that out, but it has to be contingent on the data that we see from phase I. And just to get it out of the way, what I want to see in phase I is different differentiation between doses on efficacy, on safety, and on pharmacokinetics. If I see that, then we'll have that dialogue.
So to sum up, it's very, very clear we're changing the outlook for obesity. Wegovy, we have unlocked the obesity care market, but we still see a huge unmet need and a huge need for innovation. I think we've established, both over the last couple of months, but also with more data today, that SELECT is a key differentiator. Wegovy as the only anti-obesity medication with cardiovascular and other data available to support its differentiation. And obviously, a keen eye on a differentiated competitive pipeline, and at the same time, the scalability and the supply to support that. We believe that we will continue our leadership in this space. So with that, I'll invite, my, my co-speakers, but also Karsten to the table to, moderate, Q&A.
Thank you, Martin. I see a lot of very quick hands, but just to mix things up and keep us all awake, then we'll do slightly different this time. Now, the sun is out, so we cannot use that one anymore. So now we'll start with the Q&A on commercial strategy and commercial execution. So, and then after that, we'll do development questions. So-
Can I get a chair?
So, commercial, Martin, you are the fastest. So, commercial strategy and commercial execution. Martin?
I hope my question is in the right category. But you showed the slide with the. Of course, we've seen all the strong data from SELECT and so forward, and then you go to the payers, and then they show you the slide from Capital Markets Day that only 32% of patients are on treatment after 12 months. How will you convince them to pay for something that people potentially never will experience?
I think that goes for Camilla first, and then, Doug, perhaps a comment on the 30% in the US in a supply constraint setting.
Yeah. Thanks a lot. It's clear that the more we learn about the obesity treatment, the more we know that it's a serious chronic disease. So it's basically, again, back to the SELECT data, saying that, of course, it's if you drop off the treatment, then don't get the benefits, and your weight will increase, and you may lose some of the longer-term positive effects on the comorbidities. So it's about that pattern, and actually, I think you know, well also, Martin, that we have done the study, where we after 20 weeks, people on Wegovy and placebo, and after 20 weeks, or both on Wegovy in the first 20 weeks, we let people move on to placebo. Immediately, the change in the curve was different, and people would regain the weight.
And of course, from SELECT, Martin would also say, and maybe Martin should talk to that, that it's not only the weight benefits, of course, of semaglutide that drives the cardiovascular risk reduction. But these are very important data to show that adherence to treatment is important. And we are, of course, working also on how we can support patients the best way, and maybe Doug and Mike can say something about that.
Thanks, Camilla. Doug?
Well, I would say, Martin, the scorecard is the access today, and every major PBM has covered it, and we've had really, I'd say, encouraging dialogue with payers. Our job is to describe the value proposition, and we use data to do that and to bridge beyond just weight into chronic conditions, other chronic conditions and disease states. So we'll continue to do that and use the data to our advantage. And then I'd say lastly, in the supply-constrained world, you know, we had intermittent stock-outs, and so I have to say the, you know, the stay time and the 30%, there's an asterisk to it with what we had to face last year. So as that improves over time, as we indicated it will, I think we'll see a different number.
Right. Thanks, Doc. We move to Seamus.
Thanks. So just two or one very quick question, if I'm only allowed one. The amycretin strategy as part of the commercial strategy, how important is an improved tolerability and the percentage of patients that are actually dropping off specifically for tolerability related reasons versus reimbursement or other dynamics? Thanks.
Thanks, Seamus. So, Camilla, will you take that, what we see there in the market?
Yeah. So the majority of the drop-offs actually happen in the first 12 weeks, approximately, where we see most people dropping off for tolerability reasons. And we see that with Wegovy compared to Saxenda. I think Doug showed you some the curves. There is a big difference even there as well. So you can imagine when that happens in the beginning, then in parallel, of course, it's also the expectations to the efficacy of the treatment, how long will that continue? And people are likely to stay on to the treatment, you know, as long as they continue to see improvement. So this part about tolerability is, of course, important, especially in the first phase of the treatment.
But we've also learned that management by the physician to manage expectations, that this is a likely, you can say, a drawback initially. That helps a lot, and people get used to it.
Thanks, Camilla. And, Seamus, you asked about amycretin, so this is what we see in the market on Wegovy, and the beauty of CagriSema that we have in phase three, as you know, is that we see additivity on weight loss, but not additivity on tolerability. So, I think that's really the promise of CagriSema, and then amycretin remains to be seen in later clinical trials. Great. Then we move to Pete.
Thanks, Peter from Citi . Just one question to address to, oh, sorry, Doug and Martin. Just on the commercial footprint that you have, I know you're not gonna talk about numbers that's commercially sensitive, but in terms of being right-sized boots on the ground, I mean, we all know the top line's gonna be moving, but with all this innovation, do you really need, you know, another sales force here, another sales force here, particularly in the US? Just the... I realize you can't talk to numbers, but the right sizing in terms of your current commercial footprint in both IO and US.
Yeah. Thanks, Pete. Doug first, and then Mike.
Yeah. Thanks, Pete. It's a, it's a rigorous process we go through every year when we look at, sizing, spend and control and what we need for each brand, and we'll continue to do that. So I'm not gonna get into the specifics of our strategy, but I would say as we, you know, as we view life cycle management, new indications, things of that nature, we, we size appropriately to the opportunity.
With regards to International Operations , that's probably the last thing I'm worried about. We have a really strong footprint compared to all of our competitors, ex-US, and I think we continue to, of course, assess and continue to add. I think we have a huge advantage over others that is not going to be the biggest problem.
Thank you, Mike. Now we move to pipeline and, of course, commercial. Now that we've opened it up to pipeline, and I see Sachin being fast.
Sachin Jain.
I prepped a commercial, so mine's just another commercial for that second. Jain, Bank of America. So just really big picture, as you think midterm, question I get asked very frequently: how do you think about a split of the obesity market, oral versus injectable? And within that oral, you're now thinking about two molecules, at least, a biologic and a small molecule. So geographically, how are you gonna position-
... twin oral strategy? Thank you.
That sounds like commercial strategy. Camilla?
Yeah. So, no doubt that there is a market for orals as well as injectable. Also, no doubt that efficacy is really very important in this space. When it comes to how we are going to divide, sort of, or think about our opportunities, it comes down to commercial tactics, I would say. So I, I'd rather not go into the details of that, but no doubt that we feel that across, we have a very, very strong pipeline. We showed the segments earlier, optimize, of course, the utilization of that to help as many people as possible. And I think that's, that's the closest I can get to that now. It's a relevant question, no doubt, but also a very competitive one.
Scalability is really in fashion these days.
Yeah.
Now we move to this table.
Thanks so much. Matthias Häggblom, Handelsbanken. For Martin, in light of the SELECT data, for how long can you continue to start new CV outcome trials with placebo as a control? And in a scenario where you would be asked to, would you expect your emerging obesity pipeline to be differentiated enough to be superior to Sema in such a setting?
Yeah, absolutely. So honestly, not for very long. When we start to see label updates, starting with Wegovy, and for the next five years, that's maybe where we will be. We'll have to consider what's the right comparator in this space. Specifically, vis-a-vis semaglutide, the promise of CagriSema is better weight loss, better glycemic control, but also better on markers of cardiovascular disease. So that wouldn't be a concern to us. But right now, actually, for CagriSema, our first trial will be against placebo, because when we started the trial, SELECT was not available.
Thank you, Martin. Then we move back here.
Thank you very much. Question, please, for Doug, on U.S., prescribers. You showed some nice numbers, that these are growing quite dramatically. Can you comment on the proportion of those that are specialists versus primary care? I think probably increasingly important, given the huge demand and the long waiting lists that we hear for patients to see specialists. So are you yet seeing broader physician adoption?
Doug?
Yeah, it's a good question, and we are seeing broader adoption, as evidenced by the slide. And I would say that generally speaking, we still see 80% of the prescriptions coming from HCPs and nurse practitioners, and then the other 20%, there's a lot in between that some specialists. We did deploy a couple of years ago a cardiovascular team. We're happy we did that, and we'll continue our efforts across specialty as well as primary care, which in the end is an enormous opportunity for us in terms of that segment.
Right. Then, we move here to Marcus Shaw .
Thank you. Mark Purcell from Morgan Stanley. Martin, could you help us understand how you move the physician and payer audience from weight loss to outcomes? And in your CagriSema comments, you talked about looking at lower doses of CagriSema, whereas you're looking at high doses of Sema 7.2 with pivotal data later this year. So can you help us understand this sort of dose effect in terms of obviously weight, but quality of weight, you know, CV factors, inflammation, triglycerides, et cetera? Thank you.
So I don't think I said lower doses for CagriSema. Currently, we are investigating 2.4 + 2.4. And we actually see a potential if the 7.2 mg of semaglutide pans out to go into even higher doses with CagriSema in the lifecycle management space. So we are investigating everything, but currently, we see the maximum benefit on weight loss, on glycemic control, but certainly also on the cardiovascular biomarkers on the doses that we picked for phase III, so 2.4 and 2.4. I think specifically to your first question, I think we're only allowed one question?
Yeah.
But, um-
One answer.
Communication, sharing of data, we are super happy with the publications that will get out, but also more specifically, the guideline updates and the regulatory updates that will entail. It will enable our medical communication, but also when we get the regulatory updates, our commercial communication.
All right. Then, we move to Michael Novod.
Thanks. Michael from Nordea. A question to Doug. So we see today that Cigna is saying that you have signed, also Lilly has signed, new deals around commercial access to obesity drugs, where you also have sort of a, a financial guarantee and a cap. So can you give a bit more flavor to that, and how does that correlate with sort of, a financial guarantee, likely driving higher volumes in a world where there's supply constraints?
Yeah. Thank you, Michael. It's a good question. What I would say is we're open for business, and what that means is, is that we, we know that one stop, one shop is not gonna be the answer to the amount of patients that we want to serve. Integrated solutions will be a part of that. So as you see in these partnerships, I don't want to get into those specific details, but we are working across all pairs right now on various different programs and services, because we know that what we're looking for is a sustainable market over time, and, and it's important to us to serve as many patients as possible. So we're off to a good start. We'll continue to keep our doors open for that dialogue, and that's just another example of vertical integration or integrated solutions, I should say.
That is one that we'll continue to pursue.
Thanks, Doug. Then let's move to Florent, the next table. Mike, could you pass-
... Ah, sorry. Thanks.
Thank you. Florent Ce spedes from Société Générale. A question, Martin, on SELECT. Based on data available so far, have you identified some subpopulation that would benefit the most from the product? That's something that could help, let's say, better access and better reimbursement, probably in Europe. So any color on that would be great. Thank you.
I actually think the strength of semaglutide is that, as far as—I mean, and we are still looking into the data. As far as we can see, if we stratify by age, by gender, by region, by duration of whatever comorbidity, we see the same benefit with semaglutide. And most specifically, actually, if we look at BMI, a patient with a BMI 27-30 has the same CV benefit as a patient with a BMI above 40.
Perhaps just adding to the response, Mike, on reimbursement in Europe vis-à-vis SELECT. What's the latest experiences in the markets?
It's going incredibly well. I just wanted to say that. Of course, we've talked to a few markets only, but I can bring news from, you know, the discussions we've had with the Swiss authorities, for example, last week. It is really about SELECT, and it is really about that there is a so-called secret sauce in Wegovy that goes way above just weight loss. And that should matter. It should matter because as you get older, then you often die from some of these conditions that you speak to. You die from a kidney failure, a liver problem, you die from cardiovascular issues. And that matters more than if you have two kilograms more or two kilograms less at the time of death.
And the payers are listening to that.
Great. Sounds good. So unfortunately, I'll have to cut the session now. So now it's lunch break. You can catch the team outside during the break, and then looking forward to seeing you back after the lunch break. Thank you.
Thank you.
My bones feel like they're being crushed from the inside. Instead of my red blood cells being round and squishy, mine are actually hard and shaped like a letter C. 17 million people globally live with sickle cell disease. The scientific research, the treatment, the knowledge is very limited. My name is Chanique Elias , and I want to change that. I've had so many complications just because of sickle cell. We need to acknowledge the scale of this disease and give it the attention needed. Sickle cell predominantly affects Black people. Did you know? Because it doesn't get much attention. I want to change the way people see sickle cell: doctors, researchers, fundraisers, pharma. I want people to pay attention. I want to make the invisible, visible.
Good afternoon. Welcome back. Good evening for those who are online abroad. It's a pleasure to be with you today, and I hope you had a great lunch and had a set of great discussions with the management and, of course, between you. My name is Ludovic Helfgott, and I will have the pleasure to walk you through what Novo Nordisk is doing in terms of rare disease. I would like to start a bit where we left together a couple of years ago when we did the last CMD, and I would like to frame a little bit what Novo Nordisk is doing from a rare disease perspective, and why we are investigating in this area. Let me start with the most important, the unmet need.
Right now, today, you have roughly between 8,000 and 9,000 rare disease in the world, out of which 95% of them don't have a proper cure. It's reduced life expectancy, severe comorbidities and impaired quality of life, long diagnostic lead times, and of course, broken continuum of care. We need to do something here. It's also part of our purpose. In that frame, Novo Nordisk has a long-standing legacy in terms of rare diseases in two aspects, particularly. First, on the growth hormone side, since the early 1970s, when the investigation started, and of course, in hemophilia, since the early 1980s, with NovoSeven first, but then all the subsequent treatments that are now helping our patients, Esperoct in hemophilia A, Refixia, Rebinyn in hemophilia B. So there is a need, there's a frame, there's a legitimacy.
Second, we really believe that rare disease constitutes an amazing opportunity for Novo Nordisk for three reasons. Reason number one, it's a strategic portfolio play. When you look at the overall portfolio of Novo Nordisk, a lot of prevalent, highly prevalent disease, and we saw that this morning. Here we have a very specialist play. Few patients, huge unmet needs, very specialized healthcare base, with physicians being both investigators and clinicians, and very specialized frontline teams on the commercial side, on the medical side. A complete different business model, so very helpful from a strategic perspective. It's also a platform to spearhead new trends. As we heard this morning, with rare disease, Novo Nordisk is working on new therapeutic platforms like a gene editing, that we are really, really spearheading for the whole company.
Innovative access pathways, of course, with early access schemes that are multiplying across the globe, not just in the U.S., not just in Europe, but also in China, for example. And of course, new operating models where we can actually clusters some centers together. And doing this by focusing not on the medicine, but on the solution around the medicine, what we call 5D, which stands for Digital Diagnostic Device, Drug, and Data, is actually a turnkey solution that is now important in the rare disease world. Was actually important already 15 years ago in the oncology world, and we believe will play a key role going forward, even in the prevalent diseases. Last but not least, it's an integrated unit, mostly dedicated to rare disease, from early research down to commercial, that is really able to work in an agile and flexible way.
So that's why we believe it's a good opportunity. When we saw each other last time, we were at the, the beginning of this adventure, and, and we spent the last few years really building our rare disease strategy that is based on three pillars. First pillar: serve more. And by serve more, I mean, what are the areas, the disease areas, in which we need to focus? As I mentioned, 9,000 rare diseases, it's very easy to get lost. It's very easy to get lost in the maze of rare diseases. So where do you pick your battles? And we decided to move from hemophilia to rare blood disorders and from growth disorders to rare endocrine, because these are the two places where there is a high growth over the coming years, but also where we're legitimate because we have the biology and we have the platforms.
The second pillar is find more, and this is very, very important again, because find more means two things. It means, one, we, we are actually allowed to pick in the best technology platforms that Novo Nordisk has to offer. Of course, the historical peptides and proteins, but also, as you can imagine, a silencing RNA, and we've just launched the Rivfloza in the US. Gene editing, I mentioned, and small molecules, for instance, with the acquisition of Inversago Pharma last year. It also means that we need to grow on both legs, both internal and external. So it's very important to grow on both dimensions. And last but not least, the third pillar is grow more. Because if we are very competitive in diabetes and obesity, we need to be equally competitive when we're talking about rare disease.
There's no reason why patient share and market share are not valid, and I'll share with you examples about that a bit later. This trajectory was built on three episodes. The first one was from 2019 to essentially 2022. We had to relaunch the search engine and really maximize the value of the existing brands. The second step in this journey is a step where we're gonna launch the new medicines that we are just bringing to patients today. And of course, we're talking all new in hemophilia A and B with inhibitors. So Sogroya in growth disorders, Rivfloza, rare hepatorenal disease, hyperoxaluria, just launched recently in the U.S., and of course, the one you're all expecting, I guess, Mim8. We will talk about a little bit later.
At the end of the decade, we'll be talking much more about the expansions towards hemoglobinopathies, sickle cell disease, and thalassemia, as an example. So let's quickly get through the first pillar: serve more. And I mentioned to you that the point was here to find the right balance between fully leveraging our experience and the logical adjacencies with our core areas, like hemophilia and growth disorders, but not spreading ourselves too thin. And this is why we came with that approach. We call it the sunshine, the rare disease sunshine, where you can see that by focusing on rare blood and rare endocrine disorders, we've decided to focus on a few disease areas, where we believe that the depth of our portfolio will be very important and our platforms as well.
Out of the sort of 350 million patients suffering from rare disease in the world, this is only 6%. 6%. So it could seem wide. It's actually very focused when you think about it. And we're focusing on 3 elements to start with, the beginning, the core, the foundation. The first one is, of course, the rare bleeding disorders, hemophilia, Glanzmann's, on which we've been already very present. Huge unmet need, very attractive growth over the next decade. New technologies coming in, including gene editing, but not just met. And we have here with Mim8, a key card to play. Hemoglobinopathies, the second one in the blood side, sickle cell disease, thalassemia, and this is really an important one.
We barely talk about it, but essentially, if you have sickle cell disease, your life expectancy is reduced by 25 years. 25 years less than the average, okay? It was around a bit more than 20 in the early 1980s. We're now around 40 today. It's a massive unmet need. And on this one, we actually are developing a portfolio in research and in development to help us tackle what we believe will be a very growing category. Last but not least, the growth disorders, the one we are already on. We used to be with Norditropin, and we're now entering with the long-acting growth segment with Sogroya. And let me now move to the second pillar of the strategy, and you've heard a lot about Martin's darlings this morning with amylin.
He's gonna talk to you a bit more about the other darlings of Martin. So what about... what's in the pipeline of rare disease, Martin?
Thank you very much. And Ludovic is exactly right. I have three kids. I love them all, and I can love more than one drug. So obviously, moving into the rare disease space, I also have my darlings. Ludovic already talked about this. In rare disease, broadly speaking, the unmet need is incredibly high. We still see unmet need in rare endocrine disorders. We still see unmet needs in rare blood disorders. From a research, but also from a development perspective, what we do is to think about how do we create synergies? By allowing ourselves to stay, for example, within rare endocrine and doing research and external innovation in that space, we can already now see in the preclinical pipeline, stuff coming in from Marcus that will be very exciting. We do the same thing in the rare blood disorder space.
We've been many, many years in the hemophilia space, but building on the synergies, the capabilities that we have in research, in development, but also in the commercial space, allows us to successfully build and progress a pipeline. So we moved from hemophilia to now also focusing on hemoglobinopathies. Ludovic talked about sickle cell disease, huge unmet need, not only in terms of decreased life expectancy, but a life in pain, a life with comorbidities, and really a huge unmet need. Rare disease from a research and development perspective is also an area where we can allow ourselves to experiment, both in terms of how we do research. We actually see more technologies applied, including gene editing, in this space than what we do in the diabetes and obesity space so far.
Actually, as Marcus also alluded to, there is a potential of also using some of these technologies in our broader disease areas, but we can maybe start out testing and learning in the rare disease space. In the development space, we do the same. Mim8 is a good example of that. It's one of the fastest development, full development programs that we've conducted in the development space, four years from first human dose to end of phase III. So right now, in the rare endocrine space, from a clinical perspective, we are investigating new indications for Sogroya. That is incredibly important. Big unmet needs in those spaces. In the rare blood disorder space, you see actually a quite broad pipeline focusing on not only hemophilia, but now also sickle cell disease and thalassemia.
I also have to mention, while it's not in the slide, Rivfloza, our first siRNA approved drug for the treatment of primary hyperoxaluria. In this slide, I wanna call out, obviously, Mim8. I'll do a little bit of a deep dive in Mim8, but I do also just wanna call out etavopivat. Talked about the huge unmet need in sickle cell disease. Etavopivat is an externally acquired molecule, and we are very excited about that. When doing development in rare disease, I talked about the speed with which we have progressed Mim8, but you also have to do innovation in terms of trial design. You don't have a lot of patients to put into clinical trials, and therefore, you have to get the best out of everything that you do. So the FRONTIER 2 trial is a reasonably complex trial.
It's not the biggest trial in the world, but we are investigating patients coming from, from a on-demand treatment, investigating patients coming from prophylaxis treatment, investigating once weekly and once monthly dosing. Mim8 has the potential to be best in class. Obviously, we have to show that in phase III, and no, I have not seen the data. They will come soon. I have not seen the data. But the potential of Mim8, based on phase II, is that it could have best efficacy. So obviously, median annual bleed rate of zero, that is to be expected. But in opposition to what we already see out there in the market, Mim8 has the potential of having zero bleeds in more than 70% of the patients. Obviously, again, I have to show that in phase III.
It has the potential to be very safe, but also a clear differentiation on convenience. So truly once monthly, in an easy-to-use device, subcutaneous injections in low volume, and therefore pain-free. Also, on the convenience side, an important differentiator. And therefore, I think Ludovic can work hopefully a lot with that.
Thank you very much, Martin. And I would love to quickly finish by the third pillar. We said, "Find more, serve more, find more," and now let's grow more. And you're gonna start by saying, "Well, grow more. What happened last year?" And I think a very fair question. If you look at our growth pattern since 2020, we actually grew in 2020, in 2021, in spite of, of course, the pressure on, on, Novo Seven, and in 2022, +1%, and we decreased in 2023. And that essentially is due to a product supply and manufacturing output crisis that we had by changing an old factory to a new factory while the demand was actually going extremely fast.
That actually created some disruption from a PS perspective, from an out perspective, mostly on the endocrine side, and we hope that the whole production will be stabilized during the course of 2024. The point, though, is that growing, of course, relies on commercial. I would like to spend a bit of time on what has not been affected by the Norditropin issue last year. It's actually the blood franchise. And you can see that actually on the left-hand side of this slide, where in the hemophilia B segment, we actually were able to double our market share in only one year. If you look at our latest launches in terms of EHL, extended half-life, the combined growth here is above 30% growth, even four years into the launch.
So it's really something which is quite impressive, and that's a tribute to the teams of Doug and, and Mike. On the right-hand side, something very interesting. Sogroya, new long-acting growth hormone. We launched at the beginning of the summer in the U.S. In less than six months, we are the third entrant on the market. We're now the number one. We have actually 6-point-something market share. At the end of the period, we're already number one, and if you look at Japan, if not mistaken, we're also around 8% by the end of the year. So as you can see, the commercial engine beyond is actually very healthy, and this is why we're so really, really confident about the promises to capture the fair share of the rare disease market.
So, as a conclusion, strategy is unchanged, focusing on rare blood and rare endocrine, a dedicated rare disease unit with early and late pipeline and launch. And last but not least, the Mim8 results, phase results expected in the first half. And if everything's fine, we might have a couple of other opportunities to talk about this later in the year. Thank you.
... The number of Martin's darlings is actually numerous this afternoon, and it's my pleasure to call Martin back to talk a little bit about cardiovascular. This side of you is really unknown.
Oh, thank you very much. Now I've really started to get into problems. Actually, it's a good problem to have. And the more darlings I can have, the better our patients and the better off is Novo Nordisk. So when we talk about cardiovascular and emerging therapy areas, we are very specifically talking about cardiovascular, liver, renal, and neurodegenerative disorders. We are active in those spaces from a research, from a development, but also from an external innovation perspective. This is part of our future growth, an important part of our future growth, and you already saw from Dave and Lars the priorities that we put in particular on the cardiovascular space.
The way, again, that we go about this in research and development is thinking about the synergies that we can do in research and development, understanding the underlying pathophysiology of the certain aspects of cardiovascular disease, liver disease, and kidney disease, because these aspects are oftentimes derived from the metabolic space. So again, if you look at the diagram, the overlap between diabetes, obesity, cardiovascular disease, heart failure, and we can do the same thing for liver disease and kidney disease. That allows us to create those synergies, building on our capabilities, and we see that as an incredible strength when we then also talk to Henrik and secure in good time, a proper supply chain. And again, we see that as a key differentiator moving forward.
There's a huge unmet need in this space, and I'm not gonna go through every single disease, but we've talked about it a couple of times. Globally, cardiovascular disease is still one of the biggest reasons for premature death. More than 30% of all deaths globally are derived from cardiovascular disease. Cardiovascular disease is many things, many different diagnoses, but there are pieces of cardiovascular disease that are very closely related to metabolism, our core. That's ASCVD, and there are still unmet needs in ASCVD, so atherosclerosis. We still see too many patients with uncontrolled dyslipidemia, uncontrolled hypertension, and we see a huge unmet need in the aspect of ASCVD that is derived from inflammation. We know that inflammation is a key driver in ASCVD, and actually also heart failure, and therefore, our focus on inflammation as part of this is very, very high.
You also heard that from Marcus. In the heart failure space, we think about heart failure in two different entities: heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. Specifically, heart failure with preserved ejection fraction is, in essence, a metabolic disease, closely associated with obesity, diabetes, hypertension, and a huge unmet need because virtually very few treatments available. Obviously, for us, it's nice to take point of departure in that we have semaglutide. We talked about that earlier today. Moving into a new therapy area, having a molecule already in the market that decreases the risk of MACE, improves cardiovascular, but also all-cause mortality, primarily thinking about the ASCVD space, is incredible.
But I have also today showed you data from the heart failure field, again, speaking to the power of semaglutide, and it's a really, really great starting point when moving into a new therapy area, also allowing us to build on the synergies that we have. But it doesn't stop there. We formulated a couple of years ago our cardiovascular strategy, and it's really, really comforting for us to see that we already now have assets in our pipeline that address ASCVD, dyslipidemia, inflammation, and hypertension. Some of it derived from external innovation, some of it, specifically semaglutide, obviously derived from internal innovation. In the heart failure space, we can say the same thing, and we even allow ourselves to focus on cardiomyopathy, specifically ATTR cardiomyopathy.
So, a quite ambitious pipeline already at this point in time, but I also have to say, a little bit spearheaded by semaglutide, that actually addresses a good number of the areas that we want to be active in. We know from SELECT that decreasing inflammation, and semaglutide does that, improves outcomes in patients. Ziltivekimab, which is our anti-IL-6 antibody, decreases inflammation even more than semaglutide does. In our phase II trial, we actually demonstrated a 90% decrease in markers of inflammation. At the same time, in a reasonably large phase II study, we demonstrated that ziltivekimab was safe. That's a novelty in this space. So we have high aspirations for ziltivekimab. Those aspirations are being exemplified that we are currently in phase III outcomes trials in three areas: ASCVD, heart failure, and acute myocardial infarction.
A few words on ocedurenone, external acquisition, small molecule targeting the mineralocorticoid receptor. It's third-generation mineralocorticoid receptor antagonist, and third generation means that we can actually see differentiation with ocedurenone on the efficacy side, exemplified here with a 16 mmHg blood pressure drop. But also on the safety side, being more specific, less risk of hyperkalemia, less risk of steroidal side effects. This, obviously, we intend to take quickly into the cardiovascular space, but it actually also holds opportunity in the chronic kidney disease space. So again, a holistic approach to what we do, a holistic approach to how we can create synergies, and obviously, we intend to do the same in the commercial space. So talking to that, I'm happy to invite Camilla to the stage.
Thank you, Martin. Thank you. So despite the fact that there's been so many efforts in cardiovascular disease over decades, there is still a huge economic burden in this space and a huge unmet need. You see here, the economic burden on the left-hand side in Europe, in the EU, was close to EUR 300 billion, and if you look at the right-hand side, you see we're getting close to $700 billion in the US on the burden of CVD. So huge implications for healthcare systems around the world. We have been in this field also around 10 years. We are probably one of the companies that have done the most cardiovascular outcome studies.
Since we met last time at Capital Markets Day, two years ago, we have completed four trials, cardiovascular outcomes trials, and we have also decided to initiate four new ones since then. One has already been started, and three are about to start, and Martin was talking to some of those. So this is just to say we do build on our existing pipeline to gain significant experience within this field. From a commercial point of view, the way that we are going to make our entry into cardiovascular disease is really to build on our leverage with semaglutide. So you know, and we talked to it earlier, how we're expanding the indications with semaglutide near term, and really also seeing cardiologists.
We are approximately seeing 30% of the cardiologists that we expect to see when we launch ziltivekimab and also doing on later on towards 2027. So the overlap is gradually increasing, and if we, at this point, are around 30% of the potential cardiologists that would be relevant, we of course will expect that we can increase that gradually over time, so that we are making, you can say, from an investment point of view, a safe entry into the space, getting to know the right people better and better before we launch our new, either standalone products in this space or completely new mode of actions in this space from our pipeline. So this is the way that we commercially are building on what we have, getting into a related area.
Our strategy is also backed up by a number of studies. Martin was talking to some of them in ASCVD, but also in heart failure, and you see the potential in terms of populations below here. So again, a huge unmet need. This is still the leading cause of death, as we talked about, 18 million deaths a year. This is something that we would like to make sure we can use our science and technologies to impact more positively. And of course, we also expect to have differentiators, as you can see on the bottom line here, in terms of how we actually are able to enter this market and make a difference that has not been made before, despite that many has been working in this field for many years. So that sort of ends our part about cardiovascular disease.
For now, we will have a Q&A a little bit later, but before we move away from cardiovascular disease and emerging therapy areas, we'd just like to, Martin, please come back up and talk about some of the other emerging therapy areas, especially MASH.
Yeah, absolutely. So we wanted to give you a snippet of what we're doing in emerging areas. And obviously, looking at this slide, you would think I will also, and Camilla will also move on to talk about CKD and Alzheimer's disease. For better or worse, we don't have time for that today. Doesn't mean that it's not important. It's a big focus area for us. Not a lot to talk, at least from my perspective, about in the Alzheimer's space, because we are currently conducting the EVOKE trials. They will read out next year, and until then, I will not know any more than you do. So really high on our agenda, but not something that we can talk to.
In the CKD space, I mentioned ocedurenone, but we don't have a lot of development activities, other than that and FLOW, but rather focus on both external innovation, but also micro activities in, in, in the, in the preclinical space. But for MASH, we can spend a little bit of time because here we actually see a rather robust pipeline. As you all know, this has been a crowded space. It's not so anymore. It's actually a quite slim space in terms of, of, of, of drug development, but the unmet need is still huge. Again, this is a disease that people live with, that is associated with comorbidities, specifically cardiovascular comorbidities, but also that people die from. And from, again, a research, a development, a commercial perspective, we can create synergies because this is a metabolic disease. Huge overlap with obesity and diabetes....
and that, again, allows us to build on our capabilities when we move into that space. Again, we also have to acknowledge, and this is exemplified by the top line, that semaglutide actually offers itself up as a really strong candidate that has the potential to be one of the two first drugs on the market in this space. It doesn't really stop there. Also, here in the clinical space, we do collaboration, in this case with Gilead, looking into the more advanced areas of NASH, MASH. But we also have early-stage assets, both in phase II, where we investigate FGF21, and actually also CagriSema. And we have phase I assets, addressing the broad spectrum of the pathophysiology of MASH, metabolism, inflammation, fibrosis. Just a few words on why we're excited about semaglutide in this space.
In a phase II trial, we saw a 67% decrease in steatosis. At the same time, we saw a decrease in fibrosis at a clinically relevant level. That actually allowed the FDA to give us breakthrough designation for this one study and agree with us that we don't have to do two phase III trials, we only have to do one phase III trial, because the other trial can actually be our phase II trial. Normally, FDA requires two well-powered, randomized, and controlled trials to approve a new indication. So what we're doing right now is we are in phase III, t he essence trial. It says 1,200 patients here. That's for the sort of full part one and part two of the study. The regulatory part of the study, focusing on steatosis and fibrosis through liver biopsy, is an 800-patient, 72-week study, so part one.
And obviously, the data have to be there, but that will read out during this year. That will allow us to have a broad palette of semaglutide offerings, moving into not only the diabetes, the obesity, but based on what Camilla and I just discussed, also the cardiovascular and the liver space. Very, very attractive offering, and very, very exciting. And Camilla will speak to how we will go into the MASH space from a commercial perspective.
Yeah. So, thanks a lot, Martin. The commercial potential we expect is around 22 million people from F2 to F4. So 22 million people is a lot of potential, but recently, until there has been no treatment available, the diagnostics has not been very strong. So when we are thinking about how we commercially prepare for this market, it's all about awareness. It's not easy to see if anyone is living with MASH or not. It's different from obesity in that sense. However, there are a job to do on awareness. There's a job to do on referrals to make sure that the physicians we have been talking about before are actually referring patients to hepatologists to get treatment. And then the diagnostics.
So in the diagnostic space, we are working with a number of other companies in non-exclusive agreements to make sure that we can also support that there is a development of non-invasive tests. So the NITs, the non-invasive tests, are important for us because, of course, they are a lot less invasive than the biopsies. And the complementary effects of these non-invasive tests is, of course, extremely important for realizing the potential in MASH. So that's why we are working in these partnerships. There's also educational activities. There are guidelines. There are consortia around this because it is a new, you can say, therapy area or at least a treatment area due to the history of no treatment available.
So all in all, this is efforts we are undertaking with a number of other companies to make sure that we can unleash the potential in MASH based on the data we have with semaglutide and are building also for the future in other compounds. So this summarizes our session on cardiovascular and emerging therapy areas. And just in closing remarks, in both areas, cardiovascular, but also in MASH, there is a big unmet need, and there's a lot that can be done. We have the cardiometabolic complementary competencies to launch products into this space. And with the significant unmet need, we believe that both in cardiovascular disease, but also in MASH, there's huge potential.
Of course, the next thing we are looking forward to this year is the readout on the 2.4 mg in MASH later this year. So very exciting, and we look forward to that. So with that, we will close this session, but invite the panel up for a Q&A, and last will be the moderator, I think.
Thank you to the colleagues. We are ready for the next Q&A session, and let's start here. Richard?
The pressure. Richard Vosser from J.P. Morgan. Maybe you could talk about the specific benefits related to MASH on the glucagon mechanism. We've seen some data there that seems to have maybe slightly better data than just semaglutide or just GLP-1. So just your thoughts on glucagon targeting and maybe amylin targeting with relation to MASH. Thanks very much.
So, I guess this is really a research question, but Martin, do you feel comfortable addressing that?
Yeah. So theoretically, glucagon is potentially good in MASH because it has direct effects on the liver.
... I don't think we've seen data that are hugely differentiated from GLP-1 alone, GLP-1, GIP. We are in the 70 in terms of the steatosis reduction. That means that it works. But I would still love to see some safety data. I would still love to see some fibrosis data. I know you would as well. So I think this is a big potential, but it's too early days. And we actually believe both from a timing perspective, but also from a functionality perspective, that semaglutide will make a big difference in this space. And then we have high aspirations for our pipeline, actually starting with FGF21 and CagriSema.
Thank you, Martin. Peter, over here. Yeah, Pete.
Thanks. Peter from Citi. Just one question for, for Martin. Just on MRAs. I had the pleasure of being at the Bayer CMD, on Tuesday, which sort of went slightly differently to yours today. But one area of, one area of overlap, to be fair, is finerenone. I mean, they have got good data in CVD and CKD, but they admitted it's hard work. And, you know, when you speak to the docs, you know, are you really gonna see these patients on an SGLT2, on a GLP-1, on an MRA? So can you just remind us, what is it about ocedurenone, that, if I pronounced it correctly, that is gonna differentiate you or versus, you know, the, the, the second generation from, from Bayer?
I think it's 2 things. We actually believe that ocedurenone has a really strong efficacy profile. Obviously, again, we have to show that in phase III. But specifically, the safety profile appears to be quite attractive, and specifically the hypokalemia side effects, that is a big barrier with this mode of action. We believe that Ocedurenone has the potential to be clearly differentiated.
Thank you, Martin. Any questions over here? No. We'll take Simon.
Thank you. Simon Baker from, Redburn Atlantic. Just continuing on the theme of MASH. You've clearly got a lot of shots on goal, and treatment options and potential treatment options there. But one other one I was wondering about was ziltivekimab in MASH, because there's been a lot of work on IL-6 implication in MASH. Is that something that you've looked at, either alone or in combination with the other options that you're currently developing? Thank you.
So I think it's a really good question, and obviously, inflammation is a key part of the pathophysiology that we see in MASH. Our belief is that the first step has to be to rectify the underlying metabolic derangement that is basically initiating the disease. We believe that those metabolic agents should serve as maybe the foundation for treatment. Adding then to that, and you actually also see that is in our pipeline, is potential for inflammation. And we could potentially see us pursuing more than what we already have, but then also down the line, potential for anti-fibrotic. But the starting point has to be, in our view, the metabolism.
Are there any questions for Rare D? Yeah. Michael?
Maybe it's more of a... Michael from Nordea. Maybe it's more of a sore topic on Rare D, because we've seen you have some significant struggles commercially, recently, due to lack of supply and manufacturing. So of course, it's not a Rare D R&D question, but more to when you're looking into Mim8, and coming products, how do you feel in terms of confidence levels, that you have addressed what you have had seen of challenges the last couple of years on the Rare D side, to also make a decent commercial push for new assets in the pipeline?
Absolutely. So it's a very good question. We really believe that we're putting everything we have right now in solving the issues behind our output presence, and I'm sure that later on, if you have questions also for Henrik, we can talk about that. So we really are investing, turning around, and accelerating the throughput of all our factories in the system, of course, on the Norditropin first. But what's important to see is that behind that, as I said, the commercial engine is actually very, very, very, very robust, and that's what we are seeing every day out for Sogroya, also in the growth hormone element, but as well as in blood.
Yeah. Thank you. And, Martin, you can continue, if you still have the microphone on the table.
It's gone.
It's gone?
It's maybe not so Rare D, but it's, I have to go back to the glucagon component, Martin, because you have had a triple G in development, or maybe not in development before, and you decided not to go with that, and now you have new triple G, and I suspect that you have swapped the glucagon with the GIP, maybe. Maybe you confirm that, and, and then maybe what the issues, what are your concerns regarding glucagon?
So first of all, I have to acknowledge that other players right now are moving into the glucagon space, and they appear to be successful. Based on what we saw, we actually observed some safety tolerability profiles and aspects that we didn't really like. There was actually reasonably good efficacy, not as good efficacy as we saw with CagriSema, but then we had a safety profile, specifically on cardiovascular, that was less attractive. We could potentially have overcome that, but in a pipeline prioritization perspective, it was quite easy to up prioritize CagriSema because it had better efficacy and better safety profile. And then in that aspect, then cancel the glucagon-based molecule. That I think still makes a lot of sense.
It doesn't mean that glucagon doesn't work, but in our pipeline, we had way more attractive offerings, both from an efficacy and from a safety perspective. We've actually published the safety considerations on that glucagon. I think it's also important to call out, and none of us know at this point, glucagon is also involved in protein metabolism and amino acid metabolism. And when we talk about preservation of lean body mass, I think I'm still curious to see what glucagon does to lean body mass in a weight loss setting.
Thank you, Martin. Yeah, over here.
Thank you. Seamus Fernandez from Guggenheim. So, my question is actually on the comment earlier about the interaction between the inflammasome and IL-6. Can you, Martin, talk a little bit about where NLRP3 fits in the grand scheme of things? Other people are approaching it in CNS disorders, some are approaching it as you are in cardiovascular disease, and then, more recently, we've seen some pursuit in obesity. Can you just kinda talk about the intersection or the potential intersection of those three areas?
So I'll give you a super brief answer because I think, Marcus is also very well suited, too. So maybe you if I don't give you the right answer, you can, ask it again in the final Q&A. You're absolutely right. In most of the disease areas that we move in, inflammation has a component to at least the comorbidities, and therefore, we are very, very focused on inflammation. We actually started out with semaglutide. Now, we will sell ziltivekimab anti-IL-6, and then we have NLRP3. NLRP3 is higher up in the inflammation cascade, and that has the potential of maybe having bigger efficacy impact, but potentially also, something that would warrant a keen eye to the safety aspect.
Right now, we are building a broad pipeline that allows us to investigate the different aspects in the different disease areas, starting out with ziltivekimab anti-IL-6, but also moving further up the cascade.
Thank you. Mark?
Thank you. Mark Purcell from Morgan Stanley. With CKD, I think one of the challenges is diagnosis. So apart from using your Venn diagrams and using obesity as a trigger to test people for proteinuria and other things to diagnose CKD, can you help us understand the challenges there? And Martin, do you need SGLT2s and other combination partners with your MRA for a combination approach to keep CKD? Thank you.
I think our first approach to CKD is actually starting, and we do that with ocedurenone in the DKD space. It's a good place to start because there, the diagnosis is actually quite high. The diabetologists have a keen eye to kidney disease. But obviously, moving into the broader CKD space, this is something that we have to work on. I actually know Camilla has some thoughts on that as well, because we have the same challenge when we talk about use of CRP for ziltivekimab, or when we talk about diagnosis of MASH. So this is something that we are working quite diligently on. I've seen the combination therapies, and obviously, that's something that we need to investigate.
Right now, our aim is to first investigate ocedurenone in monotherapy, and then maybe go into combination therapies. That's obviously contingent on effect remaining unmet and obviously also dialogue with the commercial.
Thank you. Sachin?
Sachin Jain, Bank of America. Just back to MASH. You focused on the MASH resolution for SEMA. Could you remind us of the fibrosis data you had in phase II and expectations for advanced fibrosis, given fibrosis has been the real focus for the competitor datasets in the last few weeks?
Yeah, absolutely. So, honestly, I can't recall the number, but I think we saw an around 50% reduction in fibrosis, placebo-controlled, that was less. And that also means that the... it was not statistically significant, but clinically relevant. That actually prompted the FDA to say, "This is still good if you can show the same thing in phase III." Because in phase III, we'll have the sample size to show statistically significance on that differential. I think more importantly, 75% risk reduction of progressing to the next level of MASH, so progressing from F1 to F2 or F2 to F3, which is obviously also very, very relevant when we talk about prevention of progressing to, let's say, cardiovascular disease or end-stage liver disease.
Any Rare D question? Yeah. Go here in the back.
Yes, Eric Berrigaud, Stifel. One clarification question on Mim8. On one slide, we see the blue arrow of the phase III going into 2025, while you're saying at the same time, the primary endpoint will report in H1 2024. Does that mean that the complexity of the trial will require that you look more into a subsegment of the data before you're gonna file? What's the time between primary endpoint availability and filing time? Is it when we're getting into 2025?
... I think so, we never really speculate on filing time. We have to see the data first. What we can say is that we'll have the phase III data in first half of this year, so within the next couple of months. And then obviously, we'll do regulatory filing as soon as we can. To the complexity of the data, honestly, I don't know.
Take a final question down here.
Thank you. Florent Cespedes from Société Générale. Quick question on rare disease for Ludovic. How do you see the dynamic of the rare disease business going forward as you have new products launches? Should it be back on the 2021 timeframe with a low single digit or something a little bit more dynamic with the new products and some production capacity coming back?
As you can imagine, we're not guiding on forward growth rate, as you can imagine. But what you can see is that we really, really worked hard to create a portfolio with many drugs in sort of adjacent indications and many launches to come. Which was not the case when in the phase 2022. But that's, again, I'm sure-
I think Ludovic is being a bit humble here. I think he showed that when we have products, we can actually compete and gain share. So I think it has potential to have an attractive growth.
Absolutely
... profile without getting specific into that. So with that, we wrap up this Q&A session, and now you have to get a bit active because 2/3 of you will have to move to the neighboring building. And there are some signs here, so if you're in Data Science and AI , Region China, it's the neighboring building. Don't worry, it's very close. The sun is shining. And then we have Region EMEA in this room. So enjoy the breakout sessions.
Am I on? Now I am.
Yeah.
All right. Welcome back, and welcome to the most popular breakout session. So congratulations on picking the most popular breakout session, which means that you didn't have to go to the building next door. So this is our Region EMEA , deep dive, and the way we feel this is through two persons. And the reason behind that is that internally in Novo Nordisk, we don't have anything called Region EMEA . We have two regions. We have SEMEA and Northwest Europe, so that's how we're organized internally. But external reporting, just to make it simpler on the external part, we call it Region EMEA .
So, this really to get a good feel for the commercial execution and operations in EMEA, and I have two superstars with me today. So, the first one to kick off is Andrej Popovski, who has been in numerous geographies on a global scale with Novo, heading up being SVP of what we call Region SEEMEA. And then following him, we have Emil Larsen, who is running Northwest Europe. So, they'll do, call it 15 minutes presentation, and then we go into 50 minutes of Q&A. So, over to you, Andrej.
Thank you, Karsten. Very good afternoon. I'm super happy that we can share together with Emil presentation to the audience, which is expecting, you know, to see what are the growth opportunities in EMEA. And, I'd like to start with. Or I will start with, diabetes, and then, Emil will cover obesity, followed by the questions. As Karsten mentioned, SEMEA, EMEA is pretty diverse region. It's cafeteria of all the, all the markets, and, you know, you can imagine different affiliates, different potential, different population. We cover 30% of the total population of IO, International Operations . And of course, you know, we are dealing with very varying local dynamics. What is very common and similar to what Mike presented, it's all about growth, and we are growing.
We see the growth of the segments. First of all, diabetes segment is growing, and within diabetes, what is growing is GLP-1, where we are gaining market share, and this is modern oral anti-diabetic treatment. Where we are present there, we are gaining market share. At the same time, if you look at the insulin market, it's flat, but if you dig a bit deeper, it's growing around 5%-6% a year, and we are holding 50% of the market share. So this is very important part of the business for us, and we want to continue successful performance there, especially that we are, we will be having icodec soon. And of course, you know, we have very high expectation in terms of launch of the product. Obesity, it's all about Novo Nordisk.
For the time being, we are growing the obesity market. So my market is growing, and of course, it's thanks to Novo Nordisk efforts, and we are looking forward to for the more and more launches of Wegovy in the coming years. That was market and how we are performing. Please have a look. In last three years, we have started to see significant double-digit growth across all the geographies. Majority of growth is coming, of course, you know, from GLP-1, both obesity and diabetes. But as I mentioned, insulin still. It's, first of all, big business for us, and secondly, it's still growing. So if you can, you can only imagine if one day we will launch icodec and start to address 10 million of the patients who are now treated with the other, let's say, basal insulin treatments.
This is very, very, very, let's say, optimistic prognosis for us. GLP-1 market. We have—we are representing 50% of the total GLP-1 share within IO. So we are pretty important geography or pretty, pretty important region, so our performance in GLP-1 segment is, is really critical. For—if you compare our market share in 2020 to 2024, we, we managed to gain around 10% market share. So market is growing, and we are growing market share within the market. If you look especially at the Rybelsus, we are very happy with the performance of, of, of our oral treatment. We have managed to gain market share within the ex, within the growing market. So let me dig a bit into Rybelsus, our oral treatment.
We have already achieved 8% of the market share in last three years, after launch of the Rybelsus, which has been launched in 30 countries in EMEA region, which represents 60% of the value potential of the region, and it's thanks to very strong commercial execution. If you look at several big markets, which we have chosen just for this session, and of course, we can discuss during the Q&A, we are very proud and very happy to see that in many of those markets, we have already achieved market leader position. These are markets where either we have reimbursement or there are markets where we are not reimbursed, we are out of the pocket, but we are still performing very nicely. Like, for example, Poland, having 17% market share, in the big oral Polish market. Italy, 28%.
I have received data today for 27 is from the previous month. So we are growing nicely, and, and that will continue in the coming years, too. Emil, now it's time to share news on obesity.
Thank you very much, Andrej. And, we are still in the Sema world, but we are shifting gears, of course, now to obesity. And Doug showed some U.S. numbers that I think have impressed everyone, including people inside the company. But, and Mike shared that the numbers are still much smaller, of course, outside the U.S. But what I can share with you is that if you look at the response from the market where we have launched so far, it's overwhelming, and it's like nothing we had dared dream of just a year and a half ago. And if we start a little bit with the outside-in perspective from the launch, from the countries where we have launched Wegovy so far, and there are eight of them there to the left of the slide.
Then you see, first and foremost, that even neighboring countries have quite a different starting point in terms of where are we with the obesity pandemic, the share at the moment. These are OECD numbers of the total adult population with obesity, so quite some differences. But what we also see, if we move into the future, that in 2030, 2035, in all these countries, we estimate that more than three out of ten will have obesity. In UAE and the UK, it'll be four out of ten. So this is, of course, a tsunami that's been going on for a while, and it's not about to stop anytime soon. So that's there.
Equally interesting, also, if you look at differences across, and you have the bar below, you will see that we have Denmark and Norway, where right now we have reached the penetration in the obese population with a BMI above 30, with GLP-1 products, and as you know, that's Novo Nordisk for the moment, and it's mainly in these two countries, Wegovy at the moment, of 7%. So if you go out on the street here and find someone with a BMI, BMI above 30, 7% of them will be on Wegovy at the moment in Denmark. If it's north of Copenhagen, you might have 12 or 13 as your average. So this, of course, has been accomplished in the span of just 1 year and a bit. It's staggering. It's like nothing we had ever experienced before.
Come to some of the other markets there, you're down in the low single-digit, maybe even below 1%. But there you will also see later, it's later obesity launches, and particularly, it's really Wegovy unlocking this potential. So it's something we worked on for almost a decade. We launched Saxenda. We built the platform since 2015, but in relative terms, the unlocking we see where we have launched Wegovy in Europe is just staggering, and in relative, it's terms like nothing we had really dared hope for. So, so quite something. We also, of course, have all wondered in all Europe, did people want to pay out of pocket? It's always been very difficult in chronic care, but this is a different business. Willingness to pay is much more than we had expected.
If you look to the right side, it's just showing that growth from a low base in the EMEA geography. In the last quarter of 2022, DKK 1 billion in sales move on just 4 quarters, DKK 1.7 billion, with just a launch into a small part of the overall obesity potential in these countries in a large geography. So quite something. Of course, what we saw and what we wanted to learn with Norway and Denmark and Iceland is what happens if we don't restrict volumes in relatively small population settings, and you saw, you saw the result. We, of course, couldn't keep on launching in large countries, given our supply situation unconstrained. So we decided consciously to say, "Okay, we wanna constrain, and we wanna learn from other geographies."... patients with high unmet needs should have the opportunity.
Of course, we also wanted to build the experience in these geographies. So countries were carefully picked as models if they could manage a constrained supply. For instance, if you gain reimbursement, can you safeguard the public channel, if you have an agreement with governments? The whole point, of course, is to drive scientific dialogue, for doctors to gain experience, for pathways to be built, and of course, also to establish real-world evidence. Internally, we've also had the chance to learn. We had, in every country we've launched, a tsunami of media requests. We've had to staff the media teams. It's almost been like a hotline. Patient support has also been, of course, geared up manyfold in these affiliates. Compliance is, of course, key in this area.
So it's really been a getting the learnings, getting up to speed to handle this kind of a pull effect that we have never experienced before as a company. So very, very interesting. Very, very positive feedback. And if we go a little bit more granular, and we start with the unconstrained first 12 months we've had in Denmark and Norway. What we basically experienced in these two countries, that are GP-driven countries, is that in every corner of Denmark and Norway, within a few weeks, we had prescriptions. After around 9 months, 90% of GPs had prescribed, and we were approaching a d- prescription average depth of 8-9 prescriptions per GP.
We also saw a lot of private clinics popping up, with a lot of entrepreneurs, actually taking on quite a bit of market share in each of these countries, that traditionally have not had any sort of services in this space. We saw, very positively, that most of the patients, where we have data, appear to be on label, sort of a mid-thirties, early thirties BMI, with the data we have. And we have typically patients with comorbidities. We have a very large real-world, database in Denmark that we get once in a while, and 80% of the patients there had a risk factor or a comorbidity. So very positively, and exactly what we'd hoped for. Adherence is also trending upwards.
It's difficult to talk about adherence because, of course, we've not reached steady state, but we have kept upping our estimates on adherence, and we are looking at around nine months at the moment, which is very good, given that we are only a little bit more than a year into the longest launches. If you look to the more capped setting, and when I say capped, it's not minute. The UK launch is still the biggest launch we've ever had in the UK, so we would have liked to have more, but it's a very meaningful launch in a country that has a big problem with obesity. But we actually have had good experience. Customers were happy. We had very close interaction, particularly with the private players in the UK.
Setting the expectations, of course, made sure that, for instance, big pharmacy chains didn't get ahead of where the supply was and did a lot of marketing activities. So it's been a very careful interaction there. So far, we are able to titrate patients exactly as one, so that if people start, they can continue to the maintenance dose and stay on treatment. Another positive is the switch from Saxenda to Wegovy, because of course, we have a pen saving there. One of the ways to solve our production issue is to move from once daily to once weekly treatments. It's wonderful for Henrik. Instead of building manyfold the production capacity, we can have many more patients with the same number of devices, because here they are shared in a European setting and EMEA. Finally, we've actually had a good start with reimbursement.
We have from the very get-go, reimbursement in the UK Mike described that. Here, the limitation is the care setting, very much in terms of uptake. It takes a very broad population that fits the NICE criteria, and we also just got news a few days back that we have a very meaningful reimbursement in Switzerland. So a good start there, and of course, we don't stop. We have the discussions in every country, because it's important for us to address that inequality in healthcare, that obviously is a concern for all involved. But it's a stepwise approach, and we can also say that the majority of the future growth in EMEA will be driven by out-of-pocket, given the willingness to pay we've seen so far. So in sum, this is really the era of Sema across EMEA.
We already have the acceleration in diabetes. It will continue. There's a lot of runway there, and we just got started with experiences that were even better than we dared hope for in obesity. And of course, we have that strong market share to build on. We have a strong infrastructure, a strong presence across the geography, and that we see as a key competitive advantage. So with that, I think we'll be joined by you, Karsten, for the Q&A.
Yeah. Thanks, Emil, and thanks, Andrej. So now it's Q&A. We have 15 minutes and yeah, so we just shoot along. We go to the back here.
Do you need me to be in the mic?
Yeah, please, because we have online viewers.
Sorry, Marshall Gordon. Could you just give us a sense of what constrained or capped really means for those launches? And when you think you're going to start, either launching more countries or lifting those caps?
Yeah. Emil?
Yes, I said constrained in Denmark, as you can see, was very flexible. Now, we take it more slow in Denmark to also give other countries the opportunity to join. But it's the biggest launch ever in the UK, and of course, we don't launch in a place where we can't follow through in the following year with that growth. So the idea is, now we are building that experience in terms of how do patients titrate through to the higher doses? What is the stay time? And it's evolving. I can say already now that we are tweaking it, so we order more high doses than starter doses, because we want to make sure that we can follow through with the volumes we have allocated centrally.
Of course, we already have plans for next year as well. So we will not, of course, tell you where are the next launch countries, and it's something we evaluate quarter by quarter, based on the uptake and honoring existing patients that have started. So it's a very good growth we have planned. We could always start more countries in commercial. We are ready when we get the supply, but it's a very meaningful growth we are planning for.
So, in practice, Marshall, it means that at a group level, we allocate a certain amount of pieces-
Mm-hmm
to Region EMEA, and to... If we talk about Wegovy. So, Emil and Andrej, they know how many pieces of Wegovy will be available this year and implicitly also next year. And then that's being allocated on a country basis so that the individual GM knows exactly the number of pieces and then has to commit to, based on the criteria you saw before, commit to be able to execute a launch based on that capacity. So, the GM will get no more, no less.
That also means perfection is index 100. Of course, in sales, normally you would want to over-perform, but there's no celebration for that at the moment. We don't want to create more demand than we can honor, of course.
Yeah. Then, we'll move to Jeff.
Hi, Jeff Holford from T. Rowe. Just because the cash pay phenomenon is a bit new for the pharma industry here, can you just give us some thoughts around will we see price inflation over time on, on cash pay? So it will be the opposite of what we normally see in these markets, or what should be our expectation?
That's a good question, now with inflation rates in society and so on. So, what are the rules?
Yeah, yeah
... vis-à-vis can we, can we change price like in the US?
There are many countries involved here. But generally speaking, when we are not in the reimbursed setting, there's free pricing. So there are opportunities to go down that route. You say our main... You know, the win-win, of course, is the more patients we have titrate up to the higher doses because we have similar linear pricing, the more value we get out of every pen as well, the better the patient experience. So that's our main focus at the moment, this early into the launch. But yes, we have in the private market setting some other pricing opportunities than we have usually with reimbursement, where reference pricing also kicks in and becomes part of the agreement.
Can you comment on, you know, have you taken any price increases on the product at all? And what would be the normal algorithm? Would it be at an annual basis you'd review pricing? Just trying to understand.
We do it more often. The only situation where we typically do it, where we do it sort of this early into a launch, is if we have currency developments. And here we have had, at least one country that has had a weak currency in, in our geography. But, but normally that's the setting. And otherwise, price revisions upwards is typically more in very inflationary countries than we've had, you know. South Africa could be an example, Brazil could be another one, that has these kind of regulations for that as well.
Yeah.
Also, when you have Turkey and-
Yeah, Turkey, Argentina, Egypt, there are markets where we can, and we do those exercises.
Mm-hmm.
Yeah. Let's stay with that table, Pete.
Thanks. Peter Welford, Jefferies. Could I just ask just with regards to the negotiations with governments in Europe, just insofar as clearly there are a lot of countries yet, which yet to have the drug, even on a private pay. You've said there's a willingness to do private pay. So I guess how do you weigh up sort of potentially a government negotiating, but then obviously your supply then gets locked, versus on the other hand, actually giving the drug to a country where it doesn't have it yet, where there are patients who are willing to pay for it? I guess there's an economic argument, but I'm thinking from the patient argument as well.
Yeah
... how you weigh that up at the moment.
We've given ourselves the challenge that every country where we launch, we would like to have at least 10% of the volume allocated for vulnerable populations. So we sort of have said that, you know, that should be sort of the, where we really aim to get everywhere. So that's the idea.
Sorry, vulnerable isn't like in the U.S., if you like, where people are... Vulnerable is, you know, I mean, I could, in the UK, if you like. If the government's willing to pay for me, I'd be vulnerable, if you like. Is that, is that right?
Yeah.
Or-
10% of our—we try and say 10% of our volume, we would like to dedicate to try and see if we could take out the financial part of the care component in a given country. So-
10% would be reimbursed, simply.
Yeah, 10% would be reimbursed of the volume.
And then-
But that's the idea.
We-
But, I mean, we have, of course, outperformed that already in Switzerland. But that's the challenge we've given ourselves.
Yeah. Which links back to what Mike Doustdar was also talking about around health equity and, and having obesity recognized in society as a serious chronic disease.
Mm-hmm.
So this is really the long-term play. If we don't get that in place across markets, then we might be able to sell a lot for a period of time, but over time, we need to have it recognized as a serious chronic disease. Yeah, let's move here.
Tom McMahon from J.P. Morgan Asset Management. Just on. You said you have 7% of the Danish obese market that you can supply. You just launched in the UK. Can you serve 7% of the UK obese population? Just give a sense as to what volumes are available.
Not right now. It's... So we are not at that point at the moment. We are, at the moment, serving around 100,000 patients, closing in on 100,000 patients-
Okay
... in the UK on an annualized basis with these monthly numbers. I think it's 95,000 at the moment. There's. We will, of course, are going to increase that, but there's some way, given the number of people with obesity in the UK, of course.
Thank you.
Let's stay with Pete.
Yeah. Thank you. Peter of C iti. Karsten, I had the pleasure of reading the annual report last week, and in the disclosures, you know, Denmark went up from, like, zero something percent to 0.8%. But when you do the numbers, that implies that growth in Denmark alone was, like, 400% last year, to almost DKK 250 million. So I just wanna make sure when we think about, is Denmark the canary in the coal mine in terms of how it's gonna play out elsewhere, or is it just home market and it's a one-off? So just can you clarify that? And then if I could come back to Pete's question, just talk to us through the sort of discussions you're having with the governments in Europe when it comes to reimbursement.
Yeah.
Where the pushback is, what's resonating?
Yeah.
That would be helpful to know.
... Well, so thank you for reading the annual report, by the way, and getting into implied sales in Denmark. Of course, the math, as you know, is when you only have one decimal and then you multiply it by a very big number, then of course, there's some swing to the math. But you're correct that we have very, very strong growth in Denmark, and I would say directionally, yes. The penetration we see in an unconstrained launch with Wegovy is really what's driving performance in Denmark. Ozempic also very, very strong in Denmark. I'd say, of course, there are demographic differences in Denmark in terms of ability to pay and so on.
So it depends on what you're comparing to, but you could say 7% of the obese population. I don't think that's unreasonable to think that could be possible in other markets also. Yeah. Simon?
Thank you.
Uh, Simon-
Sorry, back from,
Oh, yeah.
Oh.
Yeah, and maybe just to add, I mean, we've seen a very similar trend in Norway. Launched a month later, not much different than Denmark, and both not with big launch meetings, to Mike's point. We did we sort of. We had unrestricted supply, but we tiptoed a little bit into it from a pro-promotional perspective. On the reimbursement discussions, we got a little bit of a stamp of approval, we feel, from the National Institute of Clinical Excellence in the UK already in March last year, actually before the SELECT data, where they found Wegovy cost effective for a quite large population group. And again, here, the limiting factor is the setting, the specialist setting in hospitals in terms of the uptake.
So that was very important, and cost effectiveness, of course, plays quite a role, particularly in Europe. But it's of course a balance with cost effectiveness and budget impact, and that's where we also have to make sure that there's ample funding in the system, so we don't crowd out other important treatment areas. So that is a balance of finding that right population, where it's clinically meaningful, but there's also affordability from a public payer perspective.
Then we'll go to Simon, and then we take Sachin afterwards.
Thank you. Simon Baker from Redburn Atlantic. Just sticking with the UK, you said that you're annualizing at 95,000 patients. The NHS in December, in the community setting, dispensed 69 Wegovy pens. So is the market vastly private pay, or is the secondary, the specialist setting-
Yeah
... bumping that up?
Yeah.
Or is it even allowing for that?
Yeah.
Is this still a market that is heavily, heavily weighted towards private pay?
A few things about the UK. We launched in September, so it's very early days. And the private market had really been waiting for the product. We had several hundred thousand patients on waiting lists, so that was just a catch-up effect waiting to happen there. It took off. In the NHS setting, as you might be also familiar with, there's the national approval, and then there is the follow-through locally and actually in each local setting, there's also a pathway that has to be approved, et cetera, et cetera.
We estimate that the capacity, when it's up to speed in the UK for treating overall obesity patients, is maybe around 50,000 patients at the moment in the hospital specialized obesity care setting, where you're talking quite. I mean, a lot of clinics, but not that many for the population size you have. It's. There's a lot of waiting lists there for consultations overall. It's been the same with bariatric surgery, et cetera. So again, it's not the scope of the population, but it's the treatment capacity, and that's also why it's so important to get started, even in a constrained setting.
So just before we move to you, Sachin, then, then I think we should just hear from Andrej, how you're preparing to for Wegovy in some of the less affluent markets.
Mm.
You know, through what you're doing on Saxenda now and your perspective on Wegovy when volumes are coming that way.
We have several countries where we have been extremely successful with Saxenda, gaining a lot of patients. And, of course, you know, we are waiting for opportunity to launch Wegovy, and I think what gives us comfort is that, of course, you know, we have created already infrastructure, which is critical for the proper launch. And what I mean by proper launch is that, of course, you know, you need to talk to the right customers, right doctors who are well trained, right nurses, and, of course, you know, you have to go to the right clinics where they know their stuff, especially when you will provide, let's say, limited volumes compared to what explosion could be.
But it will be still very precise launch, where we will make sure that all the patients who will be enrolled on the treatment, they will continue for months to go, and then gradually new starts will happen, and then, of course, we will secure the growth, which will be like year by year ongoing with the decent uptake of new patients, but hopefully no stock outs, which are very concerning for everybody. And that's why we have to have this very precise surgical type of approach. But we are pretty well prepared-
You're ready?
Because we know, we know exactly our stuff because, of course, Saxenda was launched in many, many countries.
Great. Thank you, Andrej. The last question is for you, Sachin.
Sachin Jain, Bank of America. Just coming back on reimbursement. How are you thinking about outcome-based contracts with single-payer systems, and is that becoming a discussion? And I can just take one other one. Ex-US, you're getting a lot of out-of-pocket usage. So what—I mean, this is not typically a pharma question. What work are you doing on price elasticity of what price point will generate substantial out-of-pocket demand?
Emil?
Yeah, so one more. So the first question you said?
Outcome space.
Outcome space. Yeah. Okay. It's mainly the contracts that have been done also for Saxenda in the past, successful and what we're looking at now, that's more a volume risk-sharing approach. I would say payers are typically more comfortable with that because if we in corporate are concerned about certainty, public payers are even more, you know, around not breaking their budgets, if I have to be completely honest. So it's typically more volume risk-sharing, where after a certain cutoff point you go to the price of a comparator treatment at a lower level, or you have some other mechanism there to rein in the overall cost. That's where it's mainly going.
Outcomes, we would say, so would be so logically, but there's still some more controls built into that, and it's just not been where the interests have been so far, and also based on success and experience.
The last say, pardon?
Price elasticity.
Yeah. Right now, you could say with the, it's not difficult selling at the current price points. So, of course, over time, over the very long haul, of course, that there will be a potential if you want to go to some emerging markets, et cetera, et cetera, there will be opportunities there. We also heard discussions about, you know, being flexible on presentations, et cetera. But right now, it's more from an equity and health perspective that we build sort of entertaining price discussions than from selling the volume we have at hand for the many-
Mm-hmm
... you know, foreseeable future.
Great. Thank you. That concludes the EMEA session. Thank you to Emil and Andrej for good questions.
Yeah. Thank you.
Welcome to the Region EMEA breakout session. You got the biggest room, so the most popular session got the biggest room, and some of the prior participants, they even considered taking another round because they liked it so much. So, Region EMEA is something that we use in our external reporting. In our internal organization, Region EMEA stands on two pillars. It stands on Region North West Europe, which is headed by Emil Larsen, who will join us shortly. And then, Region SEEMEA, South Eastern Europe, and Middle East and Africa. So those are the two pillars, and the latter one is headed by Andrej Popovski.
Without further ado, we'll do 50 minutes of presentations, and then we move into Q&A session. Andrej, over to you to kick it off. Welcome.
Very good afternoon. Please keep eye contact with me because, you know, it's like in a big class, everybody's sitting at the back, and nobody's really in the front. I'm super happy that we can share with you our performance within diabetes and obesity, and some prospects for the future. But, there will be no surprise for you that our graphs will be, will be very similar to what Mike has shown, because, of course, we are part of the IO, and we are one of the biggest chunk of the IO. But let me start from, from this slide, where, you know, please keep in mind that we are representing almost 30% of the world population, but we are very diverse region. It's cafeteria of all kind of markets.
That's why we have this philosophy, market fit approach, where we want to play to outperform competition in each and every affiliate, having portfolio of the products which fit best the market needs, and of course, then we execute and try to execute flawlessly to gain share. And then if you look at the market itself, first of all, maybe diabetic market. It's growing nicely. There are two segments which are growing significantly more. It's of course GLP-1, where we are present and where we are gaining share, and there is modern oral anti-diabetes market, where we are present as well, and we are growing share. So it's very healthy performance, and it's very healthy composition of the market. Insulin represents big chunk of our business. It's our heritage.
For 100 years, we've been present, helping patients suffering from diabetes, selling insulin. So we don't forget those patients, and we don't forget this market. We are very optimistically looking forward next coming years, when we will be having possibility to launch icodec. And icodec will be revolutionary for the patients suffering from Type 2, who are now treated with the basal insulin. And within our region, we have 10 million patients treated with basal insulins. They, many of them, they will be belonging to this category of dynamic patients who will be willing to maybe switch and benefit from the once-weekly treatment. When we look at obesity, it's all about Novo Nordisk so far. We are the company which is growing the obesity market, and market is growing nicely.
As you can see, we have accelerated significantly in last couple of years. Please keep in mind that it's not Wegovy only, or it's not Wegovy, it's mostly Saxenda. So having Wegovy in the future, I think its prospects will be even bigger. One slide, how we are performing. We have accelerated our growth. In last 3 years, we've been growing double digit, and this double digit is increasing year by year, so we are very happy to see this performance. And if you zoom in, where it comes from, it comes from GLP-1, GLP-1 obesity, GLP-1 diabetes. But of course, you know, we you still see growth of insulin, 6%.
One could say, "Huh, maybe it's not as impressive as, as GLP-1." Yes, we are talking GLP-1 today, but there is a significant, you know, platform on, of insulin sales, which we have generated for those 100 years of our heritage. So 6% is a nice growth, and of course, you know, keeping in mind, once again, icodec, that's great opportunity for us. Two slides before I hand over to Emil. One, GLP-1. As, as I mentioned, it's growing nicely, and we are growing our market share. That's very important. We have managed to grow almost 10%, at almost 10% of the market share points, within 4 years. So I think it's really good performance, and it's very important for IO, because we are representing 54% of the total market, for IO.
So if we perform well, then IO is showing very good numbers. Then let me zoom into the last slide before we go to obesity, Rybelsus. Are we happy with the performance? I think we are really satisfied and proud of what we have achieved within last 3-4 years. First of all, market itself is growing. We are gaining market share, but what is the most important? In the big markets, where we decided to launch Rybelsus, we have made significant progress, and we have achieved very competitive let's say, situation. If you think about Italy, which is mostly predominantly OAD market, having 27% market share after 2 years of the launch of the product is really impressive. So why I'm saying this, that, OAD market is huge. Rybelsus is very good product. It has very, very, very good features.
It has been recognized by physicians, re-recognized by the patients, and it's reflected in our performance on the—in the markets where it's reimbursed. But please look at the bottom one, Poland. It's out of pocket. 16% market share we have achieved without reimbursement, because the features of the product are really promising for the patients. Emil?
Thank you very much, Andrej. Moving to obesity, but staying with SEMA, I can say that we've had a fantastic acceleration in diabetes with semaglutide in Rybelsus formulation and in Ozempic. But we've also looked to the U.S., of course, and the numbers that Doug presented that are phenomenally in absolute terms. But the feedback we've had from Wegovy, where we've launched, it's better than we had dared dream of just a year and a bit ago. But if we start with the outside in perspective in the countries where we've launched, then you will see OECD numbers there in terms of the prevalence in the 8 countries where we launched. And you'll see actually quite some differences even within neighboring countries, sort of hovering around just around 20 and close to 30 in the UK and UAE.
If you look at the projections from the World Diabetes Atlas going 10, 15 years into the future, this pandemic is not about to stop. There, we're looking at some of these countries, all of them having more than three in ten with obesity, and countries like the UK and UAE having more than four out of ten. So it's a pandemic that's here to stay, and that's why we're so happy to have seen that feedback from where we have launched Wegovy. And that's what you see in the bar below. That basically depicts the penetration of Novo Nordisk GLP-1s, so Saxenda and Wegovy, in the countries out of the population of obese people with a BMI above 30.
Of course, it really describes that we have an unlocking effect, a transformation of diabetes treatment in just a span of less than a year in Norway and Denmark, where we have launched unconstrained. So we have reached more than 7% of the obese population in those 12 months or so since launch. We also have areas, as Mike described, here north of Copenhagen, where if you meet people on the street, 12 or 13% of all people with obesity would actually be on our product. And even in less affluent areas, you would be at the 4%-5% mark in a country like Denmark. So it's been transformative.
We did well with Saxenda, steep growth, but this is a different ballgame we have with Wegovy, and we'll talk more about that. To the right, you just see the growth. Again, we have launched in a small part of the obesity potential in the EMEA region, and we already see a very good growth from the last quarter of 2022 to the last quarter of last year. We've seen a growth of 70% from DKK 1 billion- DKK 1.7 billion with just a few launches, and most of these launches late into the year.
But of course, we learned that with the supply situation, we could launch unconstrained in small population countries like Denmark and Norway, and gain important insights that I'll be sharing later, but we couldn't do it in large countries like the UK, with large obese populations, or Germany, et cetera. Therefore, we decided to actually take a different approach, a central volume allocation approach, where we said: We definitely wanna gain experience from other care settings. We want to create real-world evidence together with payers, for instance, and scientific experts, and basically make sure that the experience is established across the world in diabetes care little by little, as we get more volume. It's also allowed us to gain valuable internal experience, because launching Wegovy is like nothing we've ever tried before.
The phone will not stop ringing from journalists, et cetera. Customers also will reach out to us much more frequently, and of course, we need to be on top of compliance in a controversial area with that kind of demand from patients. So it's a different ballgame, and this controlled approach has actually served us well in terms of getting to many more patients across a larger geography. I should also say that while we say constrained, it's still the biggest launch we've ever had in the UK. So we are not tiptoeing into these countries necessarily. We just make it very clear to our own organizations and to external partners what are the volumes available, and success is selling exactly that and not getting patients started that we cannot follow through with in terms of titration.
So it's a difficult task, but it's a very meaningful task, and it's a task where the discussion we have with healthcare providers on a daily basis out in the field is, with a constrained amount of supply, how can we get the most health out of every scarce pen we have? And that is a very meaningful discussion, of course, that, that to have at the moment, but, but, super, super interesting. I'll share a little bit some of the learnings we've had. And to the left side, you have the learnings from the first 12 months, where in Denmark and Norway were unconstrained on the volumes, but still careful in terms of how much demand we created. What we saw was that in every corner of Denmark and Norway, within just a few weeks, we would have prescriptions.
We have 90% of GPs in the two countries as prescribers, and many of them we had not had interactions with before we launched, so a lot of them also called us for education, et cetera. So a whole new universe opening up with a lot of breadth and actually also a lot of depth. So, so the average number of prescriptions in Norway, we estimate, is around 8.5 or so per GP, and in Denmark, more than 80% of GPs have had more than 8 scripts. So breadth and depth instant compared to what we've seen with any other launch in the past. We also seen a lot of private clinics popping up.
There's already been a strong setting for, for private pharmacy chains in the UK, but in a country like Denmark, it's not been the tradition, but we've seen that channel opening up with, with quite some speed as well. The positive experience has been overall, that despite the speed of the uptake and the patient volumes, the data we have suggests that patients are actually very much on label. So in Denmark, we have a large real-world database that we got in September, 90,000 scripts or so, and we could see that 80% of the patients had a comorbidity or risk factor. We have a bit more sporadic data on BMI, but the data we have also suggests early to mid-30s in terms of BMI as the average.
Then on adherence, it's almost too early days to talk adherence, because what is adherence half a year into a launch or even a year? Because the patients that could take you up, in terms of average, have not been around for so long. But we are now keeping on modeling longer stay time and sort of hovering around nine months in a Danish setting at the moment, but of course, hoping it will increase over time. This is quite impressive in a Danish system. In chronic care, patients have not been used to paying out of pocket. We tried over the years across Europe, by the way, to make patients pay just a little bit of copay for innovative treatments and not been very successful in diabetes.
It's a completely different game here in terms of willingness to pay. So quite interesting and a lot of good learnings in that, and we are actually very positively surprised by adherence, where we keep tweaking also our supply, so we supply more of the higher dose presentations of Wegovy to all the markets. In the UK and the other early markets that we came in with here in the fall, Switzerland included, we actually had quite good feedback on the controlled launch, where early on, we made it clear to partners what was the supply they could expect. Doctors knew approximately how many scripts could we honor, and also externally, the sentiment has been positive. So we are happy with that decision. We also saw a surprisingly fast switch from Saxenda to Wegovy.
That's a wonderful switch in terms of a product upgrade, but it's also a big help, of course, to Henrik and the product supply organization, because we go from a once weekly treatment or once daily to once weekly treatment, and it's the same pen. So instead of building many more factories, which we should also do, by the way, we get an extra help here by serving a lot more patients with the same number of pens. Finally, we have actually been positively surprised by reimbursement. We had it from the get-go in the UK, a broad population, with a stamp of approval from the National Institute of Clinical Excellence, can hardly get any better in terms of cost effectiveness assessment. And the limiting factor basically being the care setting, being specialist clinics in hospitals.
So we had that from the start, and only a few months into the Swiss launch, we launched in November. We just, by the first of March, secured quite broad reimbursement, as Mike showed, BMI of 28 with a comorbidity or above 35. And again, the limiting factor is the specialist setting, where probably we can see around a capacity of 50,000 patients a year or so in Switzerland. So good experience so far. We're not stopping there. We're having reimbursement discussions across, and maybe we can touch upon that in the Q&A. So overall, in diabetes, we have a lot of momentum in GLP-1. In the EMEA region, there's a lot more to go for also there. And you could say with obesity, we had a good early experience with Saxenda, but we haven't seen anything yet, really.
We're just touching the tip of the iceberg, but the tip looks very, very promising. So with that, let's move to the Q&A, and I think you will guide that, Karsten.
Yeah. Thanks, Emil, and so now we're moving into Q&A. 15 minutes. This is a good opportunity to get some real feel for what's cooking on Wegovy in Northwest Europe. But don't forget the entry slide on obesity and the market in some of the less developed markets in Middle East and Africa. So yeah, we go here. Emily?
Hi, Emily Field from Barclays. Just a question on stay time. So you said, I think you said in Denmark it's nine months. So given that it's an unconstrained supply environment, what are the primary reasons for patient discontinuation?
Yeah.
Do you expect that 9 months to grow over time?
... Yeah, so we don't, right now, we don't yet know exactly why people stop. I mean, we could have - of course, we have some early answers. We've always had in GLP-1 treatment, side effects, not everyone tolerate. And we have also had anecdotal, of course, issues around cost. So, so, so that's part of it. The 9 months, we do hope will increase over time. We have a little bit had a small part of the patients with a private insurance that ended towards the end of the year, so we'll see - we'll get some sense of what does that mean in terms of price sensitivity in the coming weeks and months, but it's a bit too early to speak to. Yeah. Mark?
Thank you. It's Mark Purcell from Morgan Stanley. Could you sort of help us understand the mix you expect between the out-of-pocket and the reimbursed markets? Obviously, Saxenda is a yardstick, but it's only 18 countries, I think, and it didn't have the SELECT data in it, so the balance between reimbursed might obviously be higher. Then, what's the sort of price delta we should think about as well? I think it's over $200 out of pocket, but we can see the price of GLP-1s in UK database, for example, and it's significantly lower than that. So just be helpful to understand mix-
Mm-hmm
... between the two channels and price deltas between the two channels, please.
Yeah. So perhaps if you both, Emil and Andrej, you covered.
Yeah, I mean, across the line, share of growth by far will come from out-of-pocket, because the willingness is so overwhelming to pay at the current price point. And we have only started in a small corner from a population perspective of this vast region. So even if we are very, very successful with reimbursement, it's very hard, I think, for the foreseeable future, in relative terms, to compete with that willingness to pay in out-of-pocket market.
I think it will be the same situation in some, my part of the world. When we will get Wegovy, most of the sales will come from the out-of-pocket, and of course, you know, we have this ambition as a company that wherever we launch, we would like to secure around 10% of the patients who will be getting product reimbursed with this, special reimbursement system established, you know, thanks to Novo Nordisk effort and governmental willingness. Because we would like to make sure that even in the places where we launch and patients can pay, those who really cannot afford, and they have comorbidities and, certain, you know, life situation, they get help and, will be able to treat this disease.
Mm-hmm.
Thanks, Andrej.
I think-
I heard a second question.
Yeah, on-
Was it price differential between-
Yeah
... diabetes and obesity, GLP-1? So what was your second question?
Sorry, Karsten. Yeah, it's exactly that. I mean, I think you answered the question, that most of it is going to be out-of-pocket.
Yeah.
But I think there's some reasonably big price differentials when we sort of try and think about a typical UK price discount. It looks like out-of-pocket might be, you know, twice as high as the, the-
Yeah
... price that you get from government channels.
Yeah. First and foremost, UK, in out-of-pocket setting across most countries, there's free pricing from our side. In the UK, there's also free pricing for the private pharmacy chains that drive a lot of the sales. So of course, their pricing is also very dependent on supply. So in the current situation, their margins are going up.
Yeah.
They also provide a lot of services. They lift a big part of the healthcare provision burden and do it quite well and professionally. But we do foresee that the prices will go down as supply increases at the customer level.
Uh-
On the differential between, and maybe our willingness, of course, in the public channel, you could say, I think Doug mentioned that, we're always open to talk, but of course, in the supply situation, there's a limit to the flexibility. The attractiveness of reimbursement is, of course, that the stay time is likely to go up. They will have more patients on the higher doses, which then maybe leaves room for some flexibility because it's a higher price per pen, given the higher dose average.
Mm-hmm.
So our starting point is, as we've presented earlier, it's really important for us to establish obesity as a serious chronic progressive disease, and part of that is also to work with governments to get it into local treatment algorithms, local reimbursements, government health specialties and clinics and so on. And part of that is to make certain contracts for that specific population. And I think by doing so, we really establish our brands, our products, in the appropriate way in society. So that's the balancing factor we're doing.
Mm-hmm.
Uh, Richard?
Hi, Richard Vosser from J.P. Morgan. Maybe you could talk about the... In the UK, of course, the NICE has a stay time of two years, and then you stop treatment. Post SELECT, maybe you could talk about the conversations you're having to try and lift that time limit in the UK and other markets?
Yeah
... in EMEA.
Yeah, good point, because of course, their cost-effectiveness pool was before SELECT. So, of course, we're having those discussions. But in the UK, we also, of course, have to get started first. It takes some time from the NICE approval to trickle down to the local care setting, so that's what we're focusing on now, and creating that real-world experience, because of course, we wanna show the stay time, show the hard outcomes in the real world, and then hopefully we can also address the two-year limitation down the road. But it's really a matter of getting started, also in the UK, on the ground, in these specialist centers.
It is a time-bound contract with the NHS, right? Which goes both ways in reality. So they learn how the product works in that setting. It generates real-world evidence, and then, of course, we understand how this channel works in the UK market.
... Yeah. Yeah, Henrik?
Henrik Vedel, C WorldWide. One question: How do we handle off-label use of Ozempic in obesity?
Yeah
In the markets where you, where you've not launched, Wegovy?
We have, of course, people in the field, and who very, very clearly, describe and educate on, on the correct indication. And, and, we have no... I mean, that it's, it's a, it's a big issue. We have also had a lot of general managers who've been very vocal in the media on addressing this, and we've worked with authorities, in every way to educate. If we see, let's say, private clinics, providers, et cetera, that are not living up, it could also be in obesity, by the way, to the indication, then, of course, we also notify authorities. So, so we are quite proactive there. It's impossible for us to know the exact, share of sales that are-- where this is happening, but our impression is it's quite limited.
And of course, the best solution long term is to launch Wegovy, and have that option as well, to where we should have the real discussion around serious chronic care of people with obesity, so.
The complication, of course, being that we can control the market until distribution, and we can control all our communications around the product and education around the product, for appropriate, on-label use. And then from there, it's really a medical assessment about a specific patient and whether any given product is appropriate for that specific patient. And then if we see data that is indicating misuse, then, of course, we report that, but it is ultimately a medical evaluation.
Yeah. Klaus?
Klaus Johansen at Global Health Invest. Just, maybe you could help us to understand, when you engage in a dialogue with the European authorities in each country, we have the SELECT data, but what is the second most or the third most important discussion point? How to save costs for the system.
Mm-hmm.
We have the 20% reduction, but what is the second and third most important?
Mm-hmm. Mm-hmm.
That's fine. So what's our best health economic arguments, Emil, when you talk to the different countries? And then, Andrej, perhaps you can cover in your markets afterwards.
Yeah.
I think it's a very strong argument that we decrease the risk of diabetes, where we have a very well described, well sort of understood cost setting for people who develop diabetes on top of the cardiovascular events. So reversing the risk factors and pre-diabetes is one of our key arguments. We also very much, of course, want to get into a discussion on productivity. It's not always that authorities are as receptive to that discussion as we would like, because it can also be a bit siloed between, let's say, ministries. But that, of course, is one we would very much like to drive with the real-world evidence. What is the attachment to the labor market?
Because we think there are very, very strong arguments, but that takes time, and it will also take real-world evidence to really take that discussion home. Then I would say the other part, as I said, is it's very much budget impact, of course, understanding that, making sure that on both sides of the table, we are comfortable with the volume of take, so we can honor it, and of course, payers can afford it. Andrej?
Maybe an, maybe anecdotal, one anecdote from Italy. Recently, Italian government is focusing on obesity, and, you know, we don't have Wegovy on the market, but, but they want to discuss obesity, and they want to discuss obese because they, they recognize that it's a big burden from a health perspective, but, you know, labor perspective as well. And they, they call us to the table and, you know, we, we are now entertaining discussion about, you know, future reimbursement for the cohort of patients we need-- which needs this support mostly. But that's good moment, because, you know, we, we have to establish those small groups of patients where they get support from the government. Then, of course, real-world evidence will kick in, and then we can enlarge, groups in the future.
Yeah. And I would say that, based on SELECT, we have updated our health economic modeling and looked at on above what was in the STEP trials, how does SELECT impact? And some of the bigger impacts is really on the benefits in terms of progression to diabetes-
Mm-hmm
... in terms of health economic modeling-
Mm-hmm
... heart failure, and hospitalization. So, they really drive improvement in when you look at our own internal health economic modeling. And of course, that is what we are using when we talk to the different countries about how do they get the biggest bang for the buck, so to say, and how do it kind of the budgetary impacts in terms of the appropriate patient segments for which they reimburse.
Yeah. Thomas?
Thank you. Thomas Bowers from Danske. Well, actually, just to follow up on the health economics. Will you potentially be looking into actually sharing some of the financial risk with governments in order to secure coverage on the long term?
Yeah. So first of all, we are open to many models in this respect, but it takes two to dance, so to say, in that context, and find a meaningful model. So right now, I know Emil and Andrej, you've had some real-world experiences in terms of, you know, how it works on the other side also. So what works in practice?
... Yeah, but that is exactly, of course, what we have looked at. We've also done it in the past with Saxenda, with some sort of volume, relatively simple, but volume risk-sharing agreements. And of course, it's the size of the volume, it's the thresholds before you potential discount, and of course, it's comparator you discount to, that we are debating. But it requires that we can be comfortable with that, of course, and we can see the stay time go up as part of the model, so there should be a good care setting, as we discussed. And it, of course, also requires that authorities could give us some comfort on how many patients would go into that setting that we are discussing. So it's sort of a mutual risk balancing.
But it will be one of the tools going forward, no doubt, in these discussions.
If you allow me to answer this slightly differently, because, you know, Emil is responsible for Europe. I've been traveling the world, and most of, in most of the markets, it's out-of-pocket, which is driving the growth for Novo Nordisk. And for Saxenda, it's only out-of-the-pocket, which I was dealing with in Latin America and now in EMEA. This is the first time in the, let's say, in my career, when I see that patients in Europe, they are willing to pay out-of-the-pocket. And so I think that's very important factor we should not forget, that the growth of the obesity business will be immense, and there will be more and more patients who are willing to address this disease. If there will be no reimbursement, they will be paying this from the pocket.
The way we work with the governments is I think it's our responsibility to find the right patient groups who really deserve this treatment and cannot afford, and then they should get support. But I think we should not really focus only on reimbursement, because I see your questions, you know, it's reimbursement, you know, how you play with the SELECT. I mean, we will do it, but please remember this humongous army of patients who are really waiting for the opportunity to have product and together with physicians, address their disease.
That was a really nice way to end. Thank you, Andrej, and thank you, Emil. This concludes the EMEA breakout session. Now I think we all deserve to break. Thank you for listening in.
Thank you.
... All right, good afternoon, and welcome back. Hopefully, everybody still has enough energy for us, and even though Mike insulted me earlier, I've decided to join the stage with him. Thank you, Mike. I appreciate that.
You're welcome. Let's make sure you don't stutter.
We are, we are very good friends, but we're also very competitive. So, we're gonna close this up now. Probably a lot of what you've, you know, you've heard today from, from us, you know, you're gonna hear a little bit again, and I know that we're all excited to get to Karsten and the financials, so we'll be brief. But Mike and I are excited to... We've seen this get to close up this section. North America Operations.
So what we've talked about today is really strong performance over a period of time, and, you know, I've mentioned a few times, going back to my first capital markets in 2017, then participating in 2019, and then into 2022, I think one of the things that I'm proud of, amongst many, many things, is the fact that we've accomplished what we've set out to do and what we've told you. So I think Lars, in that original Capital Markets Day, he talked about improving commercial execution, making sure we were best-in-class in launches. So that's what we set out to do, and over this period, I think we've demonstrated that over many, many, many different products. But we're also very, very proud of is the fact that we now have over 10 million patients that we're serving in North America.
So we count patients, and in our world, when you look at, I think Henrik gave a number earlier, it took us about 40 years to get to 5 million patients, and it took us about a year and a half to double that. So really a step change, and we're very proud of that. Now, it has not been easy, and I think you'll hear some of this from Mike. We share in some of these challenges and opportunities. So we have had and will continue to have healthcare reforms. That is not anything new. I was just in a conversation a minute ago about, you know, every president that I can remember has always run on some sort of reform, and I'm sure it'll happen again in just a few months from now. It's happening now.
But we've been through that, and it's part of doing business in the U.S. What we also know is we're gonna have to continue to manage supply, and we've been doing that now for several years, and I think as you just heard in some of the breakouts, especially in IO, we're getting very, very good at that. Not easy, but we're getting good at that. And I think around the world, and, and certainly in the U.S., since we're, we're a, you know, country that usually launches first, there will always be intensifying competition. Like us, they, they put a lot of marketing muscle and sales muscle into launch brands in the U.S., but we're used to that as well. But more importantly is our opportunities. As I said earlier, we really do believe that with this health crisis in obesity, we have an incredible product.
It's really a gift from R&D to us to be able to commercialize it and to be able to change the lives of, of really, hopefully, millions and many more millions of patients. As we heard from some of the patient testimonials, it really is changing lives, which is incredibly important and meaningful to us. We do believe there's still an opportunity in diabetes, and you heard that. We have strong momentum in the U.S. with Ozempic in particular, and with Rybelsus. Last year, we reported 42% growth YoY. We're also, like Mike, very proud of that product and what we're doing and what we're delivering.
In the end, we're also excited about, and sort of an internal tagline that I'll say at many, many company meetings, is that there has never, ever been a better time to be at Novo Nordisk. Because when we think about where we've been over 100 years and the opportunity that we have moving forward, we're moving into new disease states, we're in the right disease states now, and we have the right brands. So it's incredibly exciting. So just lastly, if you go back to all the way 2003, you know, we've faced healthcare reform in the past. This is not new, all the way through to the IRA, which is now. We've managed that, we'll continue to manage that. It's a part of doing business in the U.S.
As I've mentioned in several occasions now, we're, we're proud of the transformation that's happened in North America. That was the commitment early on, back in 2007-2017. We would stabilize the business, and then we would return to growth. What we're also seeing is not only in the return to growth with some of these launch brands, we are building for the future. So maybe, Mike, I would say, and before I turn it over to you, the best is yet to come.
Is that because I'm on right now?
Maybe.
I share the excitement, of course, with Doug. I've seen many of you in previous Capital Markets Day, and if you go back to actually the beginning part of this slide, there was a period where International Operations was very proud to have a sustainable business at 4%-6% growth rates, and we had it actually in our corporate aspirations for a number of years. Then our new boss kind of forced us to strive for a bit more and get to double-digit growth. And we did, I would say, and the graph again shows this.
Then the last period, despite, I think, supply challenges that we have had, despite shortages, despite that launching, which is the bloodline of our organization, has gone to a lesser number per year, we have been able to increase the growth rates even though the numbers are larger. I think we are very, very proud of that in IO. We're also very proud that the bars are becoming more colorful than a single color one. It's almost like a table that has multiple legs, and that, of course, provides the sustainability that we need in the international organization setting. I say that because when you're dealing with a lot of different countries, it is not unusual that you wake up in a given day, and then there's a challenge somewhere.
I often talk about opportunities, but I do wanna touch upon some of these challenges here, some of which are exactly the same as Doug mentioned in North America: making sure that we manage the supply situation, making sure that we manage our competitors. Our competitors are actually some of the ones you know, the famous ones internationally. But we have a lot of competitors, a lot more actually, locally, that we operate with, you know, when it comes to IO. But that last piece, macroeconomics and political instability, I also like to a little bit touch upon.
As we entered this year with two wars around the world, I have a lot of colleagues in my organization that are basically operating under very difficult circumstances, trying to get the innovations that you saw from Marcus and Martin's slides into the hands of the patients, although their life is very different than the ones we live under. At any given point of year, there are earthquakes, there are other issues that we need to manage, and it goes unnoticed. It doesn't hit the news, and the numbers continue to develop and grow. And I'm very proud that, of course, we can do that under the radar. But I thought it would be important that, of course, you recognize that, as beautiful the numbers are, it's not walk in the park.
What gives us motivation, of course, are the opportunities that are mentioned here. We are building the obesity market around the world, and no matter where we speak to this, there's a huge excitement that we're part of a new revolution. We are finally able to tell the world what we have known for a long time ourselves, that obesity is not just a lifestyle issue, that there is much, much more to it. And there are, of course, ways to help and treat so many people in need that have tried on their own for so many years and have not succeeded. GLP-1 growth, I showed, it's incredibly exciting everywhere. And of course, I hope that many of you guys had the chance to join the China breakout session. As a single country, you cannot get not excited about China.
U.S. is exciting, but China also, you know-
It was a very good session. I was in.
And then, of course, of course, when we put this in really the context of IO in a single slide, then you come with this so-called market fit approach that we have been telling you about for some time now. Regardless of what geography you're looking at, and again, we had a good session on EMEA and China, but even the rest of the world, the Asia-Pacifics and the Latin Americas of the world, follows some of this overall strategy. Now, if you look at the near term, then you see three logos predominantly: Ozempic, Rybelsus, and Wegovy. Near term for us is one or two years. As you move into the midterm, then you see a lot more Wegovy logos there because we're delayed with Wegovy, so we have to basically get as many markets on Wegovy within this period.
Obviously, then, in the longer run, it's everything that you heard about today, and some of the specificity of the various different regions comes into play here. Because while IcoSema could be incredibly exciting, let's say, in China, it might be less so in another market. But we have other, of course, engines to use as we go from one geography to the other. None of this will matter unless we turn that into some financials. And who better to explain that? The Chief Financial Officer.
Yep.
Thank you, Mike. Thank you, Doug. What an amazing performance! We're talking about historic sales growth in Novo these days, and this is really a pleasure to be able to present the finances on the back of that. So first of all, when we look at what has happened during the past two years since we had the last Capital Markets Day. I'll just try and click again here. So we had the last Capital Markets Day two years ago, and when we look at the acceleration in top line, top line growth, remember last year we delivered 36% top line growth. So almost during two years, we have doubled the top line of the company. Two years. We have quadrupled the CapEx spend over two years.
And by the way, we're gonna double it from this year to next year, or from 2023 into 2024. And the R&D investments that you've heard from Marcus and Martin, the step up we're doing there is even faster than the acceleration in our top line... and that's on the P&L. Layer on top of that, the execution you heard from Dave in our business development efforts and acquiring external innovation into our pipeline. So, so really a period of unprecedented historic acceleration for Novo Nordisk. And then you say, "What does that matter? It's only Novo Nordisk, and these are only the absolute numbers." So, we also need to look at it in a relative perspective for a similar period of time.
So when we compare to the industry, then the pace of our average sales growth during that period of time is more than double up compared to that of the industry. Our margin, significantly higher than that of the industry, our operating profit margin. And do remember, we are reporting clean numbers, so there are no adjustments in our finances, as you recall. So we're not adjusting EBITDA and core earnings and all that. This is what you see is what you get. And talking about what you get, cash return to shareholders. And so one thing is to deliver operating profit growth, but of course, it doesn't really matter unless you're able to convert that into cash flow, free cash flow, and return that to shareholders. And that's what you see in the third bar.
So, really, the cash return to shareholders also significantly higher than that of the industry. And then the last data point, and this is just a 2023 data point, return on invested capital, 89%. 89. So that is when we do our benchmarking compared to that of the industry, number one. Clear number one. So, also very, very efficient capital utilization and return on invested capital. So that's history. So what are we gonna do moving forward? This is really about how we allocate the resources we deploy in the company. And, the starting point there is simple. We start with the corporate strategy. You heard that from Lars. And, then we're super disciplined in investing behind the corporate strategy in what drives profitable growth in the future.
And we're investing on multiple time horizons, and that's what you see on the right-hand side. This is really about driving the inline assets, the on-market assets today, driving growth, diabetes, GLP-1. That's the first growth wave. The second growth wave really comes from obesity, and then hopefully also from amycretin at a slightly later point in time. Obesity is really taking off now, so investing in obesity. And then the third wave is what you heard about from my R&D colleagues and from Camilla on cardiovascular and emerging therapy areas, as well as our early pipeline. So really investing in that so we get into the third growth horizon. So really investing into growth on multiple time horizons.
So boiling that down to kind of the super, super simple version is invest in obesity care market developments, invest in expanding supply chain, and invest in pipeline. I think my job is simple sometimes, but on a daily basis, it gets slightly more complicated. So but double-clicking on our resource allocation, so how do we allocate our commercial resources into the company? I think Doug and Mike and Camilla really explained, and Ludo around, you know, how we drive the assets we have in the market. And our starting point is we have huge unmet needs, big commercial opportunities, and highly competitive assets, and that's what we're investing against in our commercial investments. So we are stepping up our commercial investments, mainly based on investing in obesity and the obesity opportunity.
That is by far the biggest investment driver in terms of our resource allocation internally. On top of that, of course, we are gradually moving into cardiovascular disease. It's mainly in, in our research and development pipeline right now, but of course, we're preparing in terms of our commercial footprint, as Camilla was explaining. So it's, it's a gradual, targeted approach, which of course, is being accelerated based on R&D pipeline readouts. And then on MASH, same principles, being driven by pipeline readouts, and of course, a targeted approach, utilizing our existing footprint, and then going focused on some of the specialist segments, like hepatologists. And then lastly, on Alzheimer's, as Martin alluded to, no news today, so that's why we call it a targeted approach.
Now we're really waiting the results from the EVOKE trial come next year. So when you put all that together, then yes, we're gonna invest more in commercial investments because we have the opportunities in terms of driving growth, short and medium term. But at the same time, we do have the commercial infrastructure in place, so we don't need more GMs in the different markets. We are already present in 80 markets today with our own employees. We have the CRM systems in place, et cetera, et cetera. So we have a lot of our commercial infrastructure in place, and based on that, then, of course, we are able to increase our commercial investments at a lower pace than we increase our top line.
So we get gearing or leverage on that front, and hence, and what we call an S&D ratio coming down in the coming years for that reason. Then on the contrary, in R&D... You heard about the opportunities we have in R&D, really about the unmet needs in society within the therapeutic categories where we are operating. And as a consequence, we see those opportunities really justifying significant investments into pipeline. Because if we are able to solve these unmet needs, then the commercial opportunity is very, very significant, and hence the return in terms of R&D investments, very, very significant. So you should expect us to continue to increase our R&D investments over and above our top line growth, and hence driving a significant step up in R&D investments. Again, it's devised through the corporate strategy, the priorities you saw earlier today.
So, so really increasing investments in Tier 1, diabetes and obesity pipeline opportunities, Tier 2, cardiovascular and rare bleeding disorders. When it comes to MASH, rare endocrine and chronic kidney disease, we believe at this point we are right-sized. It's selective, targeted investments we're doing, but with our current investments, we believe that that will not be the big moving piece, in the coming years in terms of the investment levels. And then for Alzheimer's, I put in here that it's decreasing, and it is decreasing for the simple reason that, with EVOKE reading out next year, then of course, then R&D spending is going down for that simple reason. We don't have a big portfolio of Alzheimer's projects, for good reasons.
But of course, with that magnitude of step up in terms of R&D investments, then we need to do that in a rational way. We need to ensure that we are comfortable that this will generate an attractive return on investment for our shareholders. Whereas, on commercial investments, it's simpler because it's more like a profit center mentality when you allocate on commercial investments. So in R&D investments, I've taken three pillars, and it links very nicely to what you've seen before. So on research and early development, Marcus showed it. It... This is really about expanding our early pipeline for the third growth horizon, I explained before. So expanding the early pipeline, you saw Marcus presenting an ambition about tripling the amount of first human doses.
And of course, this is not only a numbers game about, quantity, it's really, really about quality. But it's just to say that we are very focused on expanding our early pipeline. You've seen it doubling almost over the last years as Marcus presented, and with the ambition of tripling first human doses. So we do that. We allocate according to the priorities, and then, of course, we continue to focus on productivity, whether it's through AI or other means, as well as speed from start of research until first human dose. In development, given the more mature nature of the projects, then what we are looking at there, we have, I would say, a fairly straightforward governance approach, where we have a stage gate approach.
So when a project enters phase II, then of course, there's an evaluation about the opportunity behind a certain project, and with that also comes financial assessments. And the same when we go into phase III or phase III B, then there's a financial assessment coming together with the stage gate passage. And as a consequence, we have the financial assessment around the viability of our late-stage projects. And then at the same time as in research and early development, then we have productivity metrics and speed metrics in development with Martin and the team that we monitor and benchmark on an industry level. And then for business development that Dave covered, and the step up there, we have a good governance model where it comes to approval.
So we have search and evaluate, and then when we see something that we might like, then it gets into a governance setting, where we assess, is this something we want to pursue? And the assessment is basically linked to strategic fit. So does it fit into our therapeutic strategies that you just saw earlier today? Scientific attractiveness: do we believe that this is competitive technology that we're pursuing? And then thirdly, do we believe that the price required to close the deal, do we believe that that also generates value for Novo shareholders? So that's how we're governing our return on investment, on our step up in terms of R&D investments. So that, of course, yields a profit for the company, and that we're very focused on converting into free cash flow.
The free cash flow, and in terms of our capital allocation of our cash flow generated, there we have a tiered approach, also our priority approach. So first of all, our preference is to invest in the company, and of course, we only invest in the company if we believe that the investments we do generate an attractive return. Secondly, after we've done that, we are focused on returning capital to shareholders through a consistent dividend approach of around 50% of net profit per year. Thirdly, beyond investment into pipeline, linked to what I explained before. And as a last point, we have a flexible share buyback approach.
So our share buybacks, you should see as the residual of when we've done the first three, and then what is required in terms of financial reserve requirements on our balance sheet. So that may vary between years. And then you see the development over time on the right-hand side of the slide. So then a small bragging slide in terms of capital return to shareholders. So this covers the last two decades of capital return to shareholders. So over the last roughly 20 years, we returned DKK 500 billion to shareholders. So I think a lot of people, they would have liked to own Novo shares at that point in time, and then sit on them.
So, but just to say, a very consistent approach, around 50%, dividend payout to net profit, and then the residual approach on our share buyback program. And then the 2023 number with the dividend is what is proposed for the upcoming AGM, which totals DKK 9.40 dividend per share, which is a 52% increase compared to the preceding year. So a significant step up in dividend per year compared to 2022. So that's the capital allocation to shareholders. And then, net, what does that drive in terms of margins in the company when you put all this together? First of all, gross margin.
So in the coming years, with 2023 as a baseline, in the coming years, gross margin, we expect, will be flat, excluding Catalent, which... And I'll come back to that. So a flat gross margin over the coming years from a 2023 baseline of around 84%. The puts and takes behind why it's flat is we have favorable product mix, we have some negative price, and then we have impact from the elevated level of CapEx that we're running right now. So some of our CapEx projects, or for most of our CapEx projects, not all of the spending goes to the balance sheet. Some of it filters down into P&L. So putting all that together, neutral, broadly neutral gross margin over the coming years.
Then, in the light blue arrow, what you see is that assuming that the Catalent transaction closes later this year, then in the coming years, gross margin will go down. And the reason why it goes down is basically linked to amortizations and depreciations linked to Catalent. So both on intangible and tangible assets, there will be a significant step up compared to before, and non-cash, and that is what is driving gross margin down. S&D cost ratio, I explained, going down, R&D going up, admin continuing to go down, simply due to the top-line growth, combined with a platform already in place.
Putting all that together yields an operating profit margin, which is increasing, but not as much as if we'd not done the Catalent transaction, which of course, we've done for very, very good reason-reasons in terms of scaling our supply base for the medium and long term. So that covers the margin development. So in closing, accelerated sales growth, we're delivering top quartile sales growth in the industry. We have an operating profit margin above average in the industry. We have a growth and return-focused resource allocation of the company linked to our corporate strategy. And then we continue to have a consistent financial discipline, where we invest in the business while maintaining an attractive capital allocation to our shareholders. So with that, I would like to invite Lars back on stage.
I would like to invite, I think, Doug and Mike, also, to a Q&A on financials. Yeah, let's start here.
You should come closer.
Yeah, please. I don't think the microphone is on. Nope.
Try again.
No?
Maybe now.
Okay. Yeah.
Yeah.
Yeah.
Thank you very much. Florent Cesped es from Société Générale. A question on, on margin, going forward. Do you believe that, if at some point you cross the 50% threshold, even with Catalent, what, what's the risks to see at some point? You, you talk a lot, a lot about, access, market access. It's important for, for the patients, but in the meantime, when you will, talk with payers, we'll talk about budget as well. So if, obesity has become a really, meaningful, very significant market at some point, what about the conversation you could have with payers, given the strong improvement of your operating profit margin going forward? Thank you.
Yeah. Thank you. And maybe I'll actually answer that. So, we are not having increased margin as a strategic objective, to be honest. We see a dynamic, dynamics right now, where there's a very strong growth in our top line, and we are scaling, as Karsten alluded to. But it's not an objective of ours to drive margin. It's a dynamic period right now where obesity is being acknowledged as a disease. We're generating the data we hope will create that point at a price point where payers are actually willing to pay for it. But it's also clear that we are scaling our volumes to get to many more patients, and typically, as you grow your business, you get to lower price points.
And that could well be at a lower margin over time, but fueled by a bigger volume. So to succeed in serving many more patients, we'd also anticipate lower price points over time. But it's not meaningful to, say, go low on price now until the disease has been acknowledged. And in some of the conversations I've had with policymakers, when they start talking about price, I say, "Okay, let's just align on the disease first and the value of treating patients, because unless you see that as a meaningful activity, there's no price point that makes sense." So right now, we have to establish that body of evidence to have the right discussion of what is the future price point, and I think that will unlock value, volumes significantly, and that's what we're preparing for.
So, a strong business also at a lower price point in the future, and I think that will jive with the societal model that we want to operate within.
Hi. Thank you. Emily Field from Barclays. Doug, you talked about, you know, having navigated through multiple iterations of healthcare reform in the United States in the past. Generally, there's an expectation that semaglutide could be added to the Medicare drug price negotiation list for 2027. It's obviously a very different product to some of the drugs being added in 2026. Can you give us any initial thoughts on potential pricing impact there, or, you know, how you're thinking about that in the context of navigating through the IRA?
Uh, yes.
Yeah.
So, um-
So Doug, it's difficult to predict about the future, but we are getting some experience right now in negotiating with the government.
We are, and I would never predict the future there, that's for sure, because it is the government. But what I would say is this, you know, we're getting through negotiations right now with aspart. We still have a couple of rounds to go, so I really can't comment any further there. But what I would say, and what we've generally said is that one of the concerns we've had with the IRA specifically is that it could limit innovation and choice for seniors downstream, and we think that is challenging. So I don't wanna try to predict what products and when and what that impact may be, so I'd characterize it as that.
Maybe add to that, of course, compared to the aspart negotiation we have now, where there's limited volume opportunity, even at a lower price point in the U.S., there's still a significant volume opportunity. So again, establishing the medical benefits of using semaglutide will lead to, say, broader use of the product. And I think that can somehow compensate for also government negotiation. Yeah. Simon?
Okay.
Yeah. Yeah, you'll, you'll get a chance, both of you.
Go ahead, sorry.
Yeah. Simon Baker from Redburn Atlantic. Doug, you mentioned your first appearance back in 2017. I'm just looking at my notes, and three of the things you highlighted as principles for success in the US market was to integrate, localize, and focus. I just wonder if you could update us on the localized bit. You just. You said back then, the market was very heterogeneous, and you gave some examples of, I think, actually Boston and Birmingham, as very, very different places where it needed a different approach. How has that changed over time? Is the US sort of coalescing into a more homogeneous system, or is it as varied as it used to be back in 2017? Thanks.
It's good when,
Those are good notes, I tell you. Good thing I read those slides and reviewed them with Dave before we got up here. But when we reorganized, we did change part of the commercial structure because we did... You know, the U.S. is made up of, of many, many, many different pieces, and still today, and I don't know if it's getting any more homogeneous. So for us, a little bit like Mike, when we think about market fit in the U.S., we are healthcare is local in the U.S., and we're trying to meet it where it is, whether it's the health system, the employer, the local payer. And our teams, we do get vertically integrated to make sure that we are bringing our best in terms of the dialogue and the communication that we're having, in terms of the value of our brand.
I think we're still in that same model to a large degree, and I think it's still been successful.
Yeah. Thank you, Doug. Please.
Hi. Thanks. Steve Atkins from Polen Capital. I had a follow-up for Karsten. On the gross margin, I understand with the increased amortization expenses from the Catalent deal, but you should be able to pull forward more revenues than expected, right? Because of the completion of the deal, that should be an offset. Are you assuming that, or is it just because price will be a negative factor, that gross margin still may decline?
Yeah. So, clearly the reason why we do Catalent is to access more capacity faster. But the margin guidance is for the coming years, so it doesn't fully offset the step up in amortization. So if you look a little bit further out, then you're absolutely correct.
Thank you.
Thank you. Yeah?
Thanks. Matthias Häggblom , Handelsbanken. So growing at the pace you are as a corporation, you need to hire a lot more people compared to the pace you've done historically. So during 2023, I think the net number increased by some 17%, and I guess the gross number of people brought in was even higher. So how does you as an organization manage, and does it provide new risks, given the current pace of hiring?
Yeah, that's a great question, and we'll have Tania Sabroe, who is leading people and organization on the stage later on. So maybe if we could park that question for her? Because I think she's the best educated person for answering that. So we'll keep note of your question. Thank you. Pete?
Thanks, Peter at Citigroup . Doug, I'm not gonna let you get away with this sort of the Medicare sort of brush off, but-
Of course, why would you do that?
It is election year, I understand, and there's probably bigger fish to fry. But, in light of the SELECT data, in light of your competitors being a bit more vocal about, you know, it's not a matter of if, but when, is there anything you're hearing in terms of, you know, potential Medicare opening up or the appetite for that, so that bill to hit the floor? Or is it really... You know, what is your intel telling you?
Thank you for the question, 'cause it is a very important issue for us to unlock access for seniors in our country for anti-obesity medications in total. And I think that, I guess how I would characterize it is my own team, my own public affairs team, still has it characterizes as, you know, if and not or when and not if. And I think that for us, we still have more signatures. We got to get an appropriate CBO scoring, and I think that, as I continue to say, that the body of evidence that we're building and SELECT importantly, puts us in a better position, for sure.
Of course, short term, we have plenty of patients to, to target, so, we can, we can be patient on that. Yeah.
Thanks. Seamus Fernandez at Guggenheim. Just a question on the CapEx side of things. Commitment to CagriSema, complex manufacturing pen. I think in our conversations, you've actually said, Karsten, that, you know, this market can only be supplied on the injectable side, up to a certain point, but that the FlexPen and multi-dose pens are absolutely critical. Is that possible with CagriSema, or is CagriSema more of a bridge to the rest of the pipeline?
Um-
Carsten, yeah.
Yeah.
Maybe also perspective on how we see, say, lifecycle management of CagriSema.
Yeah. So first of all, what we're looking at now and the scaling we're doing on Sema alone, we're getting a lot of experience, as Henrik was covering between single-dose devices, FlexTouch, and how to balance our portfolio in that respect. And yes, in phase III, CagriSema is in the dual chamber, single-use device, and if we can get that into a FlexTouch device, that would, of course, increase scalability of CagriSema. It's not a slam dunk, but as Henrik showed earlier on, one of the aspects that we're looking at actively right now is a co-formulation of CagriSema. So it's not a dual-chamber device, but a single-chamber device.
So we are working on product development and hence scaling of CagriSema. So you should not see CagriSema as kind of a stepping stone to something coming later. But at the same time, I hope what we've shown today is the portfolio we are playing vis-à-vis the pipeline we have in obesity, where CagriSema is one play, but we have a number of other plays vis-à-vis efficacy and scalability.
Yeah. Thank you, Karsten. Martin here.
Martin Parkhøi, SEB. Just, I know we haven't talked so much about Alzheimer's today, but, given that you will see this Medicare price cut in 2027, have you advertised for, for appetite for investing in Alzheimer drug, which will be hit potentially by the same? And I guess there will be a lot of Medicare patient, in particular, for that, patient population.
Yeah, I think we can perhaps say that yes, we have, because we started it, and I think we started down that track before the IRA came about. But as I mentioned before, we are pursuing a volume strategy for semaglutide, and I think the number of indications we can expand into is actually part of also making that attractive business, despite negotiating pricing with the government in the U.S. So, we need to see the data, but I think that's part of what also makes it attractive despite healthcare reforms.
As you know, Medicare Part D is some 25-30% of our U.S. business, so it's not like we let one channel dictate, you know, how we, you know, optimize the rest of our business.
Great. Yeah. Question in the back.
Just quick to Peter Welford, Jefferies. What's the backup plan, I guess, if Catalent weren't to go through, or if there were to be, you know, from the regulatory authority, certain, you know, steps, I guess, required that you're not anticipating? And just to be clear as well, is the CapEx framework you've outlined, does that already include any additional CapEx that may be needed with Catalent, if you like? Or, 'cause I guess your financial outlook had pre and post. Just to be clear, is that irrespective really, to be honest, on the magnitude with Catalent going through?
So I can talk a bit to the strategy around Catalent and fallback, and then, Karsten, you can talk to the CapEx around that. So we can say, all along, we had a plan to build capacity in-house. You have seen that we are building significant API capacity. We had a facility coming in line in the U.S., recently. We have two ongoing construction in Denmark, so really ramping up significant API, and many of you will have an opportunity of visiting that site tomorrow. And then in parallel, we are building the fill-finish to say utilize that API. And there's a plan looking at leveraging our existing sites, and then Catalent, being a challenged company, then provide an opportunity for us together with Novo Holdings acquiring three sites.
So it's really an acceleration of what we would be able to do in-house, and that is created by leveraging, say, space they have put in filling suites that were already ordered. So it, it's accelerating that, strategy. So, and that also lies that the plan B is that we will stick to the original plan, and build that. And we have additional capacity coming in gradually over the coming years, and that will then just happen at a, at a lower pace. So we feel that's, say, a robust, plan, and of course, attractive by accelerating it. Maybe Karsten, you can talk a bit to, to the CapEx.
Yeah.
Profile.
Yeah. So, so just reiterating, so, so the base plan is that the Catalent transaction closes, and, and we form that basis on numerous external legal opinions that we did as, as part of, we and, and the other, pieces in, in the transaction did as, as part of due diligence. So, so, so that is the base plan. And, and which is hence also what is reflected in, in the CapEx outlook that, that, that Henrik explained. And, and of course, if, if, if we diverge from, from that, then, then it will entail more CapEx, internally and, and probably also more CMO agreements externally.
Thank you, Karsten. Since we are broadening out the questions, let's invite rest of management up, for full, full panel. I'll step over here, and, we'll start by addressing the people question.
Go.
And, while my colleagues come up, I'll just introduce Tania Sabroe. You haven't seen Tania on stage, before. Tania is a long time with Novo Nordisk, has spent many years, with Mike in his International Operations , and since a year or so, leading our people and organization team as Executive Vice President. So, Tania-
Thank you.
There was a question on-
Thanks
... all the new colleagues we are onboarding.
Exactly. It is correct that, of course, we are scaling, and I would say, shaping the organization in line with our strategy. That also means adding a lot of new people. Last year alone, we welcomed around 9,000 new employees. We grew around 17% in our employee base, and year to date, we are growing still around 15%. That is a lot compared to what we have been used to. You saw we are used to single-digit sales growth, and we were also used to single-digit employee growth for quite a while. But in the last two to three years, we're talking more like 12, 13, 15%, and I think that's a great opportunity. The majority of those employees are in Henrik's shop, as you can probably gather.
Around 70% is driven by the manufacturing roles, but also across the board in development, clinical, digital, we are also growing. So exciting, but also, you know, a challenge to absorb so many. So we have a keen eye on onboarding, on our purpose, on culture, on leadership, to make sure that we welcome people and also retain them. So not only that they come in, but we can actually keep them for a good period of time.
Thank you, Tania. Pete?
Peter Verdult, Citigroup. Dave, just a question for you. Now that every man, woman, and dog is trying to get into obesity, and I'm not gonna ask you to talk about targets, but just the environment to do BD now in the metabolic area. I mean, you've done some interesting deals in the last couple of years, but, you know, it's intensifying. So just, you know, is it-- Are you finding it more difficult to find, you know, good deals that are attractive, both from a clinical sense and commercial sense and, and valuation?
Yeah. Thank for that, Pete. It's a dynamic space right now, right? Every couple of weeks, we update our trackers, and there's new programs that have been added to that. But our focus is to ensure that it aligns with where we think the obesity market is going and aligns with our internal strategy. And so we're very diligent about, does this add to what we have internally? You've seen some of that today. It's a high bar. And the valuations, you know, are certainly increasing based on what they see this market. We think there's opportunity for us to still use external innovation to add to our obesity pipeline, and we'll continue to do that.
Yep. Thank you. Yeah, in the back.
Hi, good afternoon. Rajesh Kumar from HSBC. You just touched on the point on M&A, in answer to Peter's question. If, let's say, the market scenario for your ob- you know, current consensus numbers for your obesity drug plays out, there will be a lot more cash flow coming out of Novo Nordisk than you can reinvest through R&D, right? One question: Do you have, would, would you revisit the thresholds on IRR you have set for reinvestment into M&A? Or did, did you compare it with share, you know-
... share buybacks. How do you compare it with share buybacks in terms of that capital allocation piece? i.e., do you stick to your four core therapeutic areas, or do you actually step out because you think the, that would be in better interest of shareholders than buying back shares or some, you know? Just any thoughts on that would be much appreciated.
Yeah. So let me maybe start and then Karsten, you can maybe comment a bit on capital allocation. So we strongly believe in making a strategic choice based on capabilities, and in that lies also an ambition to, over time, broaden capabilities. And you can see from Marcus's presentation, that we have a strong hold in the classical Novo Nordisk peptide protein area, and we're gradually expanding that. We also believe there's value in a relative tight focus on disease areas, and we actually believe that we are broadening the options in that space. And it's not likely, with a successful execution of that strategy, that you'll see us be very aggressive on M&A.
Because we believe the biggest return we can generate for our shareholders is actually doing the value creation inside Novo Nordisk, complemented with external innovation, like you have seen us do increasingly. And I'm actually pleased with the team's ability to pick assets that, you know, at least looks to turn into, to valuable additions to the pipeline. Obviously, this is, you know, a tough space with, you know, certain likelihood of success. But I think we can, we can actually demonstrate that we're both capable of coming up with in-house innovation, but also complementing that with external innovation that is meaningful, and then we deploy our own capabilities to, to maximize the value. And then maybe, Karsten, you can always debate how smart it is to buy shares back with the price as they are today.
As the CFO, how do you argue for that?
No. So I say, coming back to my strategic capital allocation, tiering that I presented in my slide, share buybacks are number 4, and BD is Tier 3. And I'd say we have assessed a lot of BD opportunities over the last few years, and the vast majority of opportunities that dropped off, they dropped off due to strategic or scientific reasons, and not due to IR thresholds. Not that we don't have the IR discipline or the valuation discipline, but the vast majority drops off for other reasons. So yes, share buyback, that's a residual, that's... We don't want to have excess cash on our balance sheet, then we buy back shares.
But that we only do after we invested in our business, we paid dividends, and we executed on attractive BD opportunities within our strategic therapy areas.
Thank you. Richard?
Richard.
Yeah.
Just coming back to Richard Vosser from J.P. Morgan. Just coming back to the new formulation of CagriSema. Given we know that the pH is different from the two products, I mean, can we just get a bit more detail on how you're gonna work through that? Given that was, I suppose, previously thought nearly impossible.
Yeah. So I don't think we can go into a lot of details around that. I trust you understand that. But it's clear that we don't mention it on the slide, unless we see a way to actually test this out in a clinical trial. So you should assume we'll do that, and then we'll see how that plays out. Thank you. Mike?
Michael Novod from Nordea. Just another two-part question. On oral semaglutide, has always, or last couple of years, been sort of 25, 50 mg, pending appropriate commercial availability of supply. Where are we standing now on sort of the pending part, 2025, 2026? When is it appropriate to sort of fully launch 25, 50 mg?
Yeah, should I give that a crack also? Because... So the way we look at it, we are building, say, a really broad portfolio of optionality, and I think also a deep portfolio. So I think we can play to win in the injectable space, based on what you have seen today. Highest efficacy and also scalable products. And I think we can also play to win in the oral space, but you have to distinguish here a bit between the different technologies we have. If you take the SNAC-based innovation, oral Sema or oral amycretin, obviously it has a lower bioavailability compared to when we go injectable, so it takes more API.
So we look at that as an opportunity for us to win, say, in higher priced markets, where we can win on efficacy. I think we have the opportunity of demonstrating by far the strongest efficacy compared to what we see being developed. But it's not a technology that lends itself for being, say, the dominating global rollout. That will have to be injectable.... That's also why we have acquired Inversago, which is, in our view, real small molecule. So something that's really scalable, also compared to what you see out there in terms of small molecule GLP-1 place, and we actually believe it will have an attractive efficacy point. Obviously, there's a safety event to be cleared.
So when we look at that broad portfolio, we are looking at our options and also how the market will develop. And I actually think we have what is required to win in the different segments. But we would like to make the trade-offs, as we have the full data set also on the high-dose semaglutide data that we'll be reading out, and then play with that portfolio to win in the different markets. Yeah. Mark?
I just, I just stole it.
Okay.
Martin Parkhøi,
Yeah, we know you, Martin.
Exactly. Just a question for the two guys in the middle, and you can arm wrestle around the volumes that you get. But it seems like, you know, there's been a big difference between the growth rates in the two markets, because back in 2019, you had to help Doug with some muted guidance, we can say, and now it's Doug who's in the driver's seat. When should we expect to get more balance between these two regions?
When Mike starts selling more? Is that the plan? Allocating more.
The good news, Martin, is that we're both in the same car, and only one person takes the steering wheel, so we are going straight. On a serious note, I think what is happening right now - what happened back in 2016 was a one-off event, and I think it was very nice that Novo Nordisk had the international capability and presence to be able to basically offset some of the loss of prices in U.S. What is happening right now is not unusual. We launch our products always in U.S., also partially because of regulatory affairs. And then, as that launch gets going, European launches starts, and then eventually we go to Japan and China, and emerging market follows. We are following the same principle as we've done, you know, during my 35 years here.
But of course, right now, we really need to make sure that when we are coming to International Operations , we're doing it responsibly. I would not like to launch any product on a Monday, only to run out of it on Friday. That is not what any of my general managers want to do. So we better kind of have that balance, and I do think we have a wonderful balance right now, in order to kind of wait a little bit longer and then launch properly in International Operations . I think it's balanced.
Great.
So Mike always talks more than me, and I'll just simply say it's really nice to work for an organization that puts the patients at the center, and we take that into account with allocations as well. So that's it. It's really nice to see.
Great. Thank you. Mark?
Thank you. It's Mark Purcell from Morgan Stanley. Maybe starting off with you, Martin, but in terms of the new technologies coming through in obesity, siRNA, you didn't talk about that side of your Dicerna platform today. I guess non-GLP-1 orals, which Lars, you just spoke about with Inversago, and then there's antibodies as well. Apart from Inversago, you don't appear to be playing, certainly, yet in the clinic in these three settings. So do you see those as the three settings that could be most disruptive to your business? And how do you ensure that you participate in your own disruption in terms of, you know, gaining access to these technologies or being a partner of choice, as the commercial space gets more competitive as more large cap biopharmas enter the obesity space?
So maybe, Marcus, you could talk a bit to different mechanisms, and then Dave, you can talk a bit to how you see us being a partner of choice.
Yeah, so thanks for that question. Obviously, with the siRNA space, we're opening up that world. And as you know, siRNAs have been deployed traditionally more in the rare disease space, and this is where we also see advanced clinical programs with other companies. But now, actually, this next wave is coming, particularly in cardiovascular and liver diseases, and you see MASH and LXR in our pipeline. But the next wave, we actually expect internally also, are compounds that make it from obesity and diabetes. Now, those could be, you know, liver targeted; it could be also extrahepatic targeting. So I actually feel very confident that we're in a good place here, and not only have the technology, but also the combination with the biology understanding from that technology to be real leaders in that space.
So I think, you know, watch this space, what is yet to come. So I feel reasonably good. And the value proposition here is obviously, again, precision, the ability to go intracellularly, but also to have, you know, reasonably infrequent dosing, and I think that is something very important for us to pursue.
Thank you, Marcus. Dave?
Yeah, and then I think it just comes down to the way we approach partnering here at Novo Nordisk. And when an external team has an opportunity to meet the folks in Marcus and Martin's group, they see what it was like to work with us. And we're very open in terms of the way we partner, whether it be a collaboration, it could be a license, it could be an acquisition, if that makes sense. But they really see the value of our 25 years of research in obesity. They really see the value in how we run clinical trials and keep patients on for 4 years. There's no question about our ability to supply and bring it to market. So I think we'll keep getting those calls, and we're gonna continue to listen.
Thank you. Yeah, in the back.
... Thank you. Eric Berrigaud , Stifel . It looks like the market is very happy with you not updating your midterm targets. There's one maybe where you could say a few more words. It's the DKK 25 billion obesity in 2025, since in this case it has been exceeded already. So probably there's been debate internally about to do or not to do, push and pulls. Maybe you can tell us what were the pull and push, and why we decided not to do? And then since you're doing a very detailed consensus internally, you can see that consensus is already well above the 25, and so maybe you can say if you're comfortable, very comfortable, or very, very comfortable with the 25 obesity numbers in consensus. Thank you.
Yeah. So maybe, Camilla, if you can talk a bit to how we look at the opportunities without revealing any numbers, and Karsten, you can talk a bit to how we look at providing guidance.
Yeah. So if I start on the potential, we saw today that, there is, you know, a huge number of people that are living with obesity. If you look at our pipeline, even what we have on the market right now, we have an opportunity to make a major difference. So that's what we are planning for, and so therefore, to set a specific target towards 2025 when this target expires, is maybe a very, very short term, giving the long-term opportunity that this really is. And we have been-- you know, we just focus on making sure that we continue to roll out what we have of in our pipeline, and that we continue to build our pipeline, exactly as we discussed earlier in the obesity session. That's really our focus.
Getting the exact number exactly right is less of our focus. We're really driving towards the purpose in our in terms of defeating obesity, and that's also why we are not just focusing on treatment, but has also established this prevention unit to use some of our abilities. You heard maybe about AI today also, and how we can understand more and more about this disease, so we can truly expand our presence in the field and make sure many more patients are treated. That's our focus rather than a single number.
Thank you, Camilla. Karsten, you're head of guidance.
Yeah. So, head of guidance, that's a new title. So, Eric, of course, we assessed as part of preparing for the Capital Markets Day in terms of our strategic aspirations, and that's also why in Lars's opening, he covered that we're not updating our strategic aspirations. The base reason is simply that they run until 2025. So we believe that's a meaningful time horizon to close them out before we set new ones.
So if we updated the obesity target now, then implicitly it would be guidance for 2025 sales, which, I know a lot of people would love, you know, to have an opinion about whether it's too small or too big, but, but that's why we refrain from putting in a new number. I trust you sense that we're pushing with everything we have, especially supplies, to maximize the opportunity in obesity. And then to your second part of the question, vis-a-vis consensus, for 2025 and obesity, then, as you know, we provide guidance on an annual basis, and when you look at our growth drivers, it's fairly straightforward.
If you think about Ozempic, Wegovy, and Rybelsus really explaining the majority of our sales growth as a company. We have delivered guidance for 2024, so I think per definition, then it's only a 2025 number in consensus, which I think is more on sales side to have an opinion about than to me, at least publicly.
Thank you, Karsten, and thank you to my colleagues. With that, we close the panel Q&A, and I leave the floor to you, Karsten.
Yeah, so... Good. Am I on? Great. All right, so now we're getting really close to the end of this Capital Markets Day, and having been on numerous roadshows, then I know the toll of taking time to travel and the time commitment. So just like to thank all of you to, for this commitment, and it's truly a pleasure to see all of you. So before Lars closes off, then just a few practical remarks. So in a few minutes, then we will have some tapas and a glass of wine or whatever outside.
So, good opportunity to mingle with management and ask all the questions that you didn't have the time to ask during the session. So, we have a good time after this session. And then, for your travels back, there will be a hard copy of the presentations in a small binder. Of course, it's uploaded to the website for the digital people in the audience, but some people, they still like the small booklet, so you can get that.
And then for those of you who have a deep interest in Novo Nordisk and also a deep suitcase or whatever you take, then we have acquired a number of this book, which is the history book around Novo Nordisk. So it was authored around a year or two ago in connection with our hundredth anniversary by a professor at Copenhagen Business School. So it's an outsider writing the history with a lot of research. So full access to the company's archives, and also access to some of the prior and current executives. So it's a really nice read that I highly recommend.
It's a long read also, but enjoy yourself with the book if you have the space, and then give it back to Lars for closing remarks. Thank you.
... Thank you, Karsten. So we have spent a day in the kitchen of Novo Nordisk, so to say. We started out the day by talking about our strategic choice, strategies about making choice. So we made some very deliberate choice about which therapy areas we focus on, we double down on. We have then also spent the day on discussing how we play to win in these areas, and I hope it comes across that we are very excited about the opportunities we have, and also how we are executing on our strategy. There's a lot of focus on capacity, and Henrik gave us some of the details behind that. When you look at it, we are the volume leader in the world in terms of high-volume manufacturing of high complex products, biologic medicines in sophisticated devices.
So that's a competitive advantage, and we have taken steps to invest significantly in further expanding that. And of course, you should see that as a sign of our confidence in the pipeline we have in diabetes, in obesity, short-term based on semaglutide, but obviously also CagriSema and amycretin, that we can really get through very attractive efficacy levels at known safety parameters. And, as you heard, we believe that known and acceptable safety profile also applies for amycretin. So we're very comfortable about the biologics we play with there. And, in this, say, scalable manufacturing setup, we can run through these molecules in a very, very attractive way. We are also making a play on, say, the oral route, both with a real small, small molecule, and then with a somewhat more complex SNAC-based formulation.
made a breakthrough of biologics that we believe can give us the best, say, efficacy and safety profile in the space. This is a very, very attractive proposition. In addition, we are expanding our research and early development capabilities, as, as Marcus alluded to, and we're building a broader pipeline, both in the rare D space, in cardiovascular disease, and some of the emerging therapy areas. So when we look at the growth opportunity for Novo going forward, we are very confident that we can sustain the growth in the incretin, incretin space. We can drive the volumes to serve many more patients, and we can add innovation on top of that, and that we can expand in these adjacent disease areas, where, again, we can leverage our core capabilities across the whole value chain: research, development, manufacturing, and into the markets.
So it's an unprecedented growth level we are delivering as a company, and we take that as a position of strength to invest in our business to really sustain a very attractive growth projection also for the future. And that is really living our purpose, driving change to defeat serious chronic diseases, and I think that is what it also takes to be a respected company and one that is actually seen as a partner for society in overcoming some of the most difficult, chronic diseases that the world is facing. That is indeed very motivating. So thank you for your time today. We enjoy these opportunities of presenting to you, but also get your questions, because that also help sharpening our senses, so that's much appreciated. So thanks for now, and see you outside for some more mingling.
Thank you very much.