Ladies and gentlemen, welcome to the financial statements for the first three months of 2022. For the first part of this call, all participants will be in listen-only mode, and afterwards, there will be a question and answer session. Today, I am pleased to present Deborah Dunsire, President and CEO, Johan Luthman, Executive Vice President, Research and Development, Bjørn Mogensen, SVP Group Finance. Speakers, you may begin.
Hello, everybody, and welcome to the first quarter update from Lundbeck. Thank you for joining us. Next slide, please. That's looking at our forward-looking statements. I know you've all read them before, so we'll move on to talk about the business. First quarter in 2022 has been a strong quarter, driven by the momentum behind our strategic brands. Revenue achieved DKK 4.4 billion, up 2%, up 9% in total when we adjust for the Northera loss of exclusivity. The strategic brands were up 25% in aggregate and now constitute 61% of the total revenue of Lundbeck. Vyepti continued to grow strongly, achieving DKK 170 million, and we have of course seen some benefit from the rising exchange rates. In the first quarter, we saw limited impact from the Russian war.
The EBIT reached DKK 1.2 billion, and the core EBIT margin reached 27.1%. Vyepti has continued to roll out globally and is now approved in over 40 markets, of course including the EU, where the approval was achieved back in January. We've also continued to ready ourselves for the global launch, completing the Sunlight trial, which sets us up for a potential submission in China. We've completed accrual recruitment there, and Johan will talk more about that program. With Brintellix Trintellix, we've continued to deliver on our phase IV program, achieving positive topline results in the VIVRA phase IV study, which Johan will talk about in more detail also.
We are on track to deliver the headline results from our agitation in Alzheimer's disease with Rexulti trial in the middle of 2022, and also now have a possible path for PTSD headline results within twelve months. We've also continued to make great progress with the early-stage pipeline. Now let's dive into the strategic brands in a bit more detail. Next slide, please. They are our major revenue contributors, up 25%, 18% in local currency. So all of them showed double-digit growth in Q1 2022 and were growing significantly in all the regions, 24% in the US, 38% in international markets, and 18% in Europe. We expect that strong momentum to continue into the balance of the year. Next slide, please. Vyepti growth is continuing, and we're seeing several new markets launching.
We've launched several in the first quarter in Australia, Singapore, and Switzerland. The two launches that we did in the latter part of last year, UAE and Kuwait, are looking very promising. In total, we've got a plan for around 10 launches in 2022. On track, we recently got approval in Brazil. In the U.S., we're seeing normalization of our commercial engagement. We do of course see Q1 impacted by the reset of the high-deductible plans in the U.S. But we're continuing to press forward with both in-person promotion, but also our patient activation campaign which has been in social media and other more directed media we're piloting now in a broader set of media. Next slide, please. Brintellix is showing solid double-digit growth with good growth in demand.
There's strong market uptake in international markets, including China, Brazil, and Japan, where we've reached an exceptional 6.4% market share together with our partner, Takeda. We do see increased market shares in other countries, Australia, Canada, Italy, and Spain leading the way. The news flow is continuing with the positive VIVRA trial. Next slide, please. Rexulti is also continuing to grow strongly, up 24%. There's been strong uptake in recent launches in Brazil and Italy, and the volume share has reached 3.3% in Canada and exceeds 2% in the U.S. now that we're starting to get back to a more normal, promotional cadence. We're on track for those important headline results in the middle of 2022 in Alzheimer's agitation. Next slide, please.
Abilify Maintena is also growing well, and we have seen a return to growth in the LAI market in the US. There's been solid market share gains, and it's very impressive to see that market shares in the U.K. are now up to 42%, and Italy and Switzerland are well above that 1/3 market share. Abilify Maintena continues to deliver for our patients. Next slide, please. Over to Johan.
Thanks, Deborah. We are actually making steady progress in R&D with several key events recently and more coming up in the coming year. Last quarter, we reported Rexulti as sNDA for treatment of schizophrenia in adolescents, and it was approved by FDA. However, the bigger upcoming event for Rexulti is naturally the pivotal trial readout in agitation Alzheimer's disease. As you may recall, the enrollment of patients in the ongoing trial was much affected by the COVID-19 pandemic. Through very strong efforts across the Otsuka and Lundbeck teams, we are now on track for readout in the summer. I will come back to that in some more detail in the coming slides.
As you heard from Deborah, we are also now looking forward to finally being able to have a readout in the ongoing pivotal trial in post-traumatic stress disorder with brexpiprazole. This is a program consisting of two trials that were also substantially impacted by the COVID-19 pandemic. While we have been pleased to see some partial recovery of the randomization in those trials, the more important factor is that we and our partner, Otsuka, had a very fruitful discussion with FDA, which allows the change in the design of the program. We have now possibilities to conclude the study within 12 months. For Vyepti, we have now authorized the drug in 41 markets, while review is ongoing with 12 regulatory agencies.
As part of the global rollout, we are conducting a clinical trial program to support filings in China and Japan with the SUNLIGHT, SUNRISE, and SUNSET studies that Deborah mentioned. The SUNLIGHT study in chronic migraine with medication overuse, we have reached full enrollment. We did that in mid-January, and that despite the escalating COVID situation in China. We are therefore on track for headline results from this study in the early fall. The SUNRISE study, which is a much larger study with target enrollment of 530 patients and a much larger cohort in Japan, in addition to a major proportion from China, is also progressing very well. Thus, the nice execution in those studies is keeping us on the expected timelines for regulatory submissions in China and Japan.
The strong profile of Brintellix/Trintellix has been well documented in a series of well-designed and impactful phase IV studies. Most recently, we had a readout in the VIVRE study, as Deborah mentioned. That was a direct head-to-head comparison of vortioxetine versus the SNRI desvenlafaxine. I will describe that also in some later slides. Another upcoming event is the submission of aripiprazole two-month injectable formulation. That will add to our current Abilify Maintena brand for once-monthly injections. We are looking forward to submissions to EMA and U.S. during the coming months. From our phase II pipeline, I'd like to mention 09222, our high-affinity anti-PACAP antibody, which has shown in early clinical studies to bind with high affinity preventing PACAP receptor activation. 09222 had a good trial start-up in the rather large HOPE proof-of-concept study, and it's progressing well towards the readout during H1 2023. Next slide, please.
Since the readout is now coming up in our ongoing phase III trial of brexpiprazole in agitation Alzheimer's disease, I like to remind you about this condition, which has a very common occurrence and includes an extremely troubling set of symptoms. The agitation is triggered by a range of factors, including confusion, anxiety, and hallucinations. It constitutes a very high burden on caregivers and families and the healthcare system. Due to those challenges, it is a major cause on nursing home placement. Current treatment options are very unsatisfactory, while patients are commonly prescribed older antipsychotics that are heavily sedating and causing disturbances in motor functions. Agitation Alzheimer's disease occurs in well over 1 million patients, of which the minority are in community or family care, and thus an effective treatment may delay institutionalization and escalating healthcare costs. Next slide, please.
With brexpiprazole, we are now running a third pivotal trial to support eventual registration for this indication. Data from the two previous phase III studies showed that a dose of 2 milligram per day was efficacious on the Cohen-Mansfield Agitation Inventory Scale that systematically assess agitation. This primary endpoint was demonstrated to be significantly improved at the clinical and meaningful level in the past fixed dose study or in a post-hoc analysis of the 2\ mg cohort in the flexible dose arm of the second study. It's also critical to note that the 2-mg dose, brexpiprazole was safe and well-tolerated. In the ongoing phase III trial, for which we have a readout in the summer, we're studying 2 and 3 mg doses. The study includes a higher dose range than previously.
The study finalized enrollment at the sample size a bit over target of 330 patients at the beginning of the year. Next slide, please. As you heard, we had some readouts with vortioxetine. I like to highlight the very successful set of phase IV studies we have conducted on this compound. We have previously reported studies such as the COMPLETE study that showed improvement of emotional blunting in major depressive disorder, a very interesting study which has been followed by a set of publications, and the RECONNECT study that showed good effect of the drug in major depressive disorder with comorbid generalized anxiety disorder.
We have also, which is not in this outline, reported the RELIEVE study, a real-world evidence study in major depressive disorder that showed improvements in several functional and quality of life outcomes following use of vortioxetine in regular clinical practice. The MEMORY study studies vortioxetine in patients with depression, early dementia, and that is still ongoing. We had very recently the readout of the VIVRA study. Next slide, please. The VIVRA study was a randomized comparative study exploring the role of vortioxetine as a treatment option between SSRIs and serotonin-noradrenaline reuptake inhibitors, SNRIs, a rare head-to-head study on antidepressants. The efficacy of vortioxetine was directly compared to one of the latest introduced SNRIs, desvenlafaxine.
VIVRE recruited a total of 605 patients who were suffering from major depressive disorder and had a partial response to the treatment with an SSRI for at least six weeks. Both vortioxetine and desvenlafaxine showed significant improvements versus baseline. Thus, an improvement over the partial response to SSRI, as measured by the Montgomery-Åsberg Depression Rating Scale, was shown. Moreover, vortioxetine demonstrated a non-inferiority to desvenlafaxine on MADRS. Importantly, the VIVRE study demonstrated that vortioxetine provided significant benefits versus desvenlafaxine on secondary endpoints, including remission, daily and social functioning, and also, which is very important, satisfaction with medication. I'm showing here the outcome on the Functional Assessment Short Test, FAST, in the total population, where you can see that vortioxetine has numerically, and in some instances also significantly, different effects from desvenlafaxine.
We have also obtained data showing, if anything, a better separation versus desvenlafaxine in the larger subcohort of patients that were actively working, a very important subgroup. Thus, using objective assessment, the study shows a significantly better efficacy of Trintellix versus desvenlafaxine on remission, as well as daily and social functioning. In sum, this study clearly demonstrate that patients suffering from MDD, major depressive disorder, with a partial response to SSRI are offered important clinical benefits treated with Trintellix. Next slide, please. I am excited to report progress with LU-89515, our interesting novel antibody-like molecule against CD40 ligand. We have now started clinical studies for this program, thereby accelerating our R&D strategy within neuroimmunology, one of our four strategic biological focus areas. In preclinical studies, five-one-five has demonstrated engagement with CD40 ligand, leading to decreased antibody response and circulating inflammatory markers.
Lu AG22515 is differentiated, neutralizing anti-CD40L in a way with an innovative molecular design, blocking the essential co-stimulatory interaction between CD40 ligand and its receptor. The compound includes a serum human albumin binding domain, thereby utilizing albumin for half-life extension and avoiding some of the previously observed liabilities with a traditional Fc binding domain to neonatal Fc receptors. This would potentially allow Lu AG22515 to show superior clinical features, including on the safety parameters. CD40 signaling is an established and clinically validated immune pathway, through its ability to trigger activation, differentiation, and proliferation of B cells, T cells, and several other immune cells. Modulating this pathway therefore holds great promise for treatment of a wide range of immune-driven neurological diseases, such as indications of myasthenia gravis and multiple sclerosis. Next slide, please. I'm pleased with what I see here.
We have a broad portfolio early, but maturing and very interesting molecules. In 2022 and 2023, we will see key events coming up in several programs. Naturally, big R&D effort is going into the phase III and IV activities on Vyepti, a drug that has a very strong feature and to date has provided very convincing data. In studies like the pivotal PROMISE trials, but also in RELIEVE study that shows its fast, powerful onset of action, and the DELIVER study that showed its effect in patients that previously failed on prior treatments. We are now looking forward to the SUNLIGHT trials in chronic migraine with medication overuse, as described before, as well as our indication extension activities in episodic and chronic cluster headache, our ALLEVIATE and CHRONICLE studies.
We are also seeing good progression in our research and early development transformation, where we now have a number of innovative programs progressing within our strategic areas. With that, I'll like to hand over to Bjørn for the financial updates.
Thanks, Johan. We have seen solid financial performance in Q1, and the quarter is impacted by expected but negative effect from the generic erosion on Northera. Beyond that, I see solid performance of the company with a 9% growth driven by our strategic brands. EBIT reached DKK 875 million, corresponding to an EBIT margin of 20%. Even though we in R&D, sales and distributions are in an investment phase, mainly because of the global rollout of Vyepti and the normalization of activity levels after COVID. The core EBIT margin reached 27%. We continue to have a strict focus on cost spend and also continuously optimizing our organization to match the business we expect.
As we communicated in the last quarter, the Vyepti EMA approval triggered an increase in the fair value of the contingent consideration of approximately DKK 300 million. This is expensed as financial items in Q1 2022. Overall, we see the financial performance in the quarter as satisfactory. Next slide, please. Lundbeck's guidance for 2022 is maintained. 2022 will be driven by the continued growth of Abilify Maintena, Brintellix, Trintellix, Rexulti, and the strong growth of Vyepti. Lundbeck has a foreign currency risk, mainly US dollar, Chinese yuan, and Canadian dollar. The financial guidance for 2022 is based on the current hedging rates for those currencies and includes an expected hedging loss of approximately DKK 350 million. The fair value adjustment, which I mentioned earlier, brings our expected net financial items to around DKK 500 million.
With that, I turn the microphone over to Deborah.
Thanks, Bjørn. Lundbeck has, looking out into the future, significant growth opportunities. We also have something that we announced in at our full year results that is coming up in the first half, and that is the extraordinary general meeting on our dual share structure, which we anticipate that will be in the first half of June 2022. We're looking forward to the submission of the aripiprazole two-month LAI formulation in mid-2022 in Europe, U.S., and Canada, and of course, the AAD results in the middle of the year.
The Asia program headline results for the SUNLIGHT trial will come in the third quarter of 2022, and then we hope, based on finalizing discussions with the FDA, that we would be able to read out the headline results from the Rexulti PTSD trial by the end of the year to the first quarter or the first half of 2023. The HOPE study, we also anticipate the phase two results in 2023. Important information coming through the pipeline that will drive the growth of Lundbeck into the future. With that, we'll close the discussion of a strong first quarter and move to your questions.
Thank you. Ladies and gentlemen, we will now begin our question and answer session. If you wish to ask a question, please press zero followed by one on your telephone keypad and wait for your name to be announced. Again, that's zero one on your telephone keypad now. Your first question is from Wimal Kapadia, who's from Bernstein. Your line is now open, Wimal Kapadia. Please go ahead.
Oh, great. Thank you very much for taking my questions. Wimal Kapadia from Bernstein. So I'm just curious, first question, how did Lundbeck think about the deal this week for Pfizer and Biohaven? And you know, now that all is going to be in the hands of a rather aggressive marketing machine. Now, what impact are orals having today on Vyepti? And just, you know, how aggressive is the couponing? And, you know, how do you think about the change in the hands of Pfizer? And then just tied to that, you know, where are the patients coming from? Are the majority post orals? And then my second question is just for a little bit more color on Rexulti and PTSD.
It sounds like there's been some decent progress on that front with the FDA. If you do get over the line and show good outcomes, just thinking about the growth acceleration we could see, you know, how important is this indication for the Rexulti trajectory? Thank you.
Okay. Wow. Lots of questions there, Vimal, but thanks. I'll start, and Jacob Tolstrup, our Chief Commercial Officer, will also chip in there. I guess the first thing we can say about the Pfizer deal is that we were surprised it didn't happen earlier on. The Pfizer did the deal for ex-US rights. We thought that could have been a whole co-deal. Now the whole co-deal has happened. We also know that in the marketplace, Biohaven has already been extremely aggressive. That aggressive competition is already there. Importantly, remember this is a market that is going after the entire migraine market, including the acute. From people who have one to two migraines a year, all the way through that acute setting into the prevention in episodic migraine.
That product doesn't have an indication in chronic migraine. I think we will see continued heavy promotion as there has been up till now. We'll see continued heavy couponing as there has been till now. But overall, we anticipate that the level of discussion of migraine that is happening right now will draw back into the market people who have dropped out of therapy based on not being satisfied because we know that a large number of migraine patients living with migraine have stopped coming forward for treatment because they were dissatisfied. So the overall promotion of the CGRP class of therapies will draw those people back into the migraine market. Net-net, we think it doesn't change a lot because there's already aggressive promotion in the marketplace. Jacob,
Yeah.
Like you to comment.
Yeah. I mean, not much further to add. Of course, I agree with what you said there, Deborah. I think it is a very competitive market that we're looking in right now. It's difficult to see that it can become even more competitive because there is a lot of activity going on in the migraine space already today, not only from Biohaven, but with all the competitors and all the companies that are active in the space. I don't think I will add much more to that.
Yeah. I think the one thing that we do see, you know, Vyepti, we're targeting that most impacted patient population, who are the people who are, you know, using more and more acute meds, their migraines are not controlled, and Vyepti really delivers in that setting. Anecdotally, we are hearing of people who have tried even a couple of CGRPs, either injectable or oral, who have either not achieved the efficacy they wanted or have had a tolerability issue, who have subsequently been treated on Vyepti and done well. We know that there is a big unmet need in migraine. There are. Yes, it is a competitive market segment, but we do need these different alternatives for people because not everybody is treated in the same way by one product. Going on to PTSD and the commercial opportunity.
First of all, we're glad that we'll be able to get to a headline result. As you know, we have had significant difficulty during the COVID period of finalizing the accrual to the two trials. We're hopeful that with this strategy we'll be able to finish, although it probably puts a bit of a higher bar on it. It is a high unmet medical need, so we know that it's an important market, and I think what we've said is that it's not as big as the MDD market for, you know, the supplemental addition of an antipsychotic to an MDD regimen, but it's a bigger market than the schizophrenia market. Johan wanted to comment?
I just may add, of course, we can discuss the eventual growth, but I think Deborah touched upon it. It's of course a very challenging population to treat. It's a mixed group of patients with very different causes of PTSD, and this study is run on top of sertraline, which is one of the therapies that are approved for this indication. So there are not only operational challenges with this, but also of course scientific and medical challenges to obtain an effect. We at least are looking forward to see the results of this study.
Great. Thank you very much.
Thank you. Your next question is from Martin Parkhøi from SEB. Your line is now open, Martin. Martin, please go ahead.
Thank you very much. Martin Parkhøi from SEB. A couple of questions. First to the migraine. First on the orals, and maybe that is for Johan, but although Deborah also mentioned it that tolerability and efficacy of the orals. Is it the case that maybe the tolerability issues for the orals has maybe proven to be slightly less of an obstacle than what you maybe saw in the clinical data and maybe the same goes for the efficacy side? Then also maybe that is for Jacob on Vyepti.
We see this very aggressive competitive situation in U.S., but we also hear from Deborah that the market is probably now the market opportunity is much bigger now than what we saw when you bought Alder. What do you expect outside U.S.? What kind of competitive situation do you expect to see there on the opportunity for you? Then just maybe a little bit bookkeeping for Bjørn on FX, because you are so kind to mention that the hedging loss since your full-year result has increased from DKK 200 million-DKK 300 million.
If we back that out, could you then also say how much benefit you actually see on the top line, from the improved FX situation, which I guess is quite substantially if you take the current FX rates?
Johan, would you like to start on the orals?
Yeah, I can start. First of all, I think one should look at Nurtec and QULIPTA a little bit differently. If you look at now primarily in the prevention of migraine space where we are operating, Nurtec had weaker data than eptinezumab or Vyepti. While Quelipta has reasonably strong data, but when it comes to really the strong response rates, we are also stronger there. In terms of what that means on the side effect side, Neratic looks like a slightly less troublesome side effect profile, and no one has done head-to-head of course, but looks like a slightly less troublesome side effect profile. While atogepant or QULIPTA has a little more of nausea and GI problems, and it's also hitting a little harder. It may be that tricky balance.
If you really like to drive efficacy, you may actually build up a little bit more of the side effect issues that you see with the receptor blockers.
Jakob?
On the competitive situation. I think the short answer, Martin, is that I expect something that's less competitive. That said, you will see some of the same competitors in markets outside, also. There is a timing aspect of this where we are not coming in after the others, as we've seen in some cases elsewhere. We are coming in maybe even before some of the competitors that will come in after us. There is also a question mark around pricing strategy, market access, how that all plays out in the different markets around the world. Obviously, Europe will be different than Latin America, China and so forth.
There is also a question on, for instance, sampling, which is extremely heavy in the US and depending on pricing strategies outside may also be less. I think the short answer is we do expect to see some of the same competitors around the world, but we do expect a less competitive situation than what we've seen in the US.
For your question in relation to currency impact, then, of course we are negatively impacted by our lower hedging rate. If you high level look net at that, we have a positive impact between DKK 50 million and DKK 100 million.
DKK 50 million and DKK 100 million on the top line?
Yeah.
You mean the EBIT line?
On the top line.
Correct me if I'm wrong, the US dollar is up 10% higher than last year, and you have around 50% of your sales in U.S., and that only give you DKK 50-100 million net.
We are hedging at a very low rate. Where we are, next year we will start getting the benefits, but for quarter-over-quarter, it's not a lot.
Okay. Thank you.
Thank you. Your next question is from Michael Novod from Nordea Equities. Your line is now open, Michael. Please go ahead.
Yeah, thanks a lot. Also a few questions from my side. First of all, to the key brand or the strategic brand performance in IO and in Europe, it seems like you have some very strong momentum going there. Maybe, Jacob, you can add a bit of more details of what you believe is driving the market. We have been talking about earlier on whether there could be sort of a lack on the sort of the treatment need. Is it that, you know, you're starting to see that when patients are getting back, there's been a lot of treatment that's been postponed. Is that part of what is driving this very strong momentum, or is it other reasons to IO and Europe?
Secondly, also to, maybe you could remind us on the potential impact you see now we are closer to, generic erosion, probably in Canada and Brazil. Just to remind us what you're actually putting into the guidance for 2022. A question for Bjørn. Maybe also you can remind us of, what your expectations are for net debt level by the end of 2022. Thanks.
Okay. Jacob, perhaps you'd like to comment on the strategic brands doing so well in IO and Europe. Is it those patients coming in from COVID blues?
Thank you very much, Michael. I do agree it's really strong performance that we see and something that we're obviously very proud of. There are, of course, markets where we see it's purely driven by uptake and demand. Markets like Japan, where Brintellix is doing really, really well. Our best launch ever and also measured in market share. Also in China, we continue to see strong growth for Brintellix in China, even though we are not on NRDL. That's obviously a couple of places where we see strong performance. We also see it in many other places around the world. I have in Europe, across Europe, we see strong momentum for Brintellix. Specific markets that are doing extremely well are markets like Spain and Italy.
I will say across Europe, we have very strong performance for Brintellix, and also in Latin America. We even have a little bit of downsides here and there in terms of timing of markets in the Middle East and timing of tenders and so forth. So some places it's even a little bit muted compared to what we see. I wish I could say that it is a COVID or coming out of COVID that is sort of driving this. Latest data suggests that there is perhaps a little slightly higher growth in the MDD market, what we've seen in the past, but it's too early to say.
I would also say that often sometimes we see, for instance, in the U.S., that the growth of coming back and goes to generics and doesn't go to brand. That's not exactly what we see ex-U.S. We actually see also the brands benefiting from the market growth. I would say most of what we see now is brand performance related, recognizing the great profile on Brintellix. Abilify Maintena continues to do well, and it's been tracking quite well during COVID all the way through. Last point I would make is, of course, there is a correlation also our ability to come back, the promotional activity.
In markets we are at the level of pre-COVID, and in other markets we are still a little bit below, but we're getting close to where we were in our ability to promote than we were before COVID. That of course will also help performance.
Okay. Thanks.
Yeah. I think just commenting on the what's included in the guidance in terms of the patent expiries. I think in 2022 we're expecting Brazil and, if I'm not mistaken, Mexico, and that is factored in.
Yes
... to the guidance. Canada expiry is only in March of 2023, considering the pediatric extension.
All right. Thanks. For Bjørn?
The question on net debt, we expect to land around DKK 3.5 billion.
Okay. Super. Thanks a lot.
Thank you. Your next question is from Harry Swifton from Credit Suisse. Your line is now open, Harry. Please go ahead.
Brilliant. Thank you very much. I have a clarification question on the gross margin for the quarter. We saw an extremely strong gross margin, and even if you adjust for the lower amortization, it is a notable increase year-over-year. I was hoping that you could potentially explain what is driving that. You noted the lower royalty payments in the first quarter, but what is specifically driving those lower royalty payments as I think some of the products which you pay higher royalties on, like Abilify Maintena, did very well. Is that just a timing effect? Is there a mix impact that is particularly notable? Any help on the gross margin would be helpful. Thank you.
I would expect that what is triggering you there is the Nordea amortization that we don't have included in this quarter, but had in last quarter because it's LOE now. I think that's what is triggering your number.
Even if you adjust for the amortization, difference year-over-year, it seems that it is particularly strong. Is there anything else that you could potentially highlight which is driving that?
I think it's the Onfi royalty, right?
Northera royalties also.
So-
Onfi and Northera royalties are down because the sales are down.
Next question.
Okay. Yeah. Brilliant. Good.
Next question.
Your next question is from Diana Gnau from Berenberg. Your line is now open, Diana. Please go ahead.
Hi. Thank you for taking my questions. It's Diana Gnau from Berenberg. I have a couple of questions, please. Firstly, just on the M&A, just wondering, you know, what your latest thinking is around sort of like appetite to do a bigger deal, looking into sort of like the second half of this year. You know, what are some of the sort of disease areas, you know, you know, that's currently under your radar that could be a good addition, to your portfolio, please? And then my second question is, just on sort of Rexulti and the AAD. You know, clearly the phase III readout, is gonna be the next big focus. Just wondering if you could just sort of remind us again, you know, how big of a commercial opportunity you think this indication can ultimately be.
The latest visible alpha consensus sort of is stating DKK 3 billion of peak incremental sales. You know, sort of just what is your sort of thoughts around this number, please? Then my third question is just for the Lu AF82422 asset. I noticed that AbbVie has recently dropped its alpha-synuclein program. Just wanted to get your thoughts around your confidence in your sort of phase 2 program and sort of the science behind it. Thank you.
Thanks, Diana. Firstly on the M&A appetite, we've always said that M&A is not the only tool in the toolbox. We look externally at licenses, partnerships, regional deals, and acquisitions. We remain focused in brain health and in neuroscience. We focus M&A on near-term accretive deals, looking to continue to drive revenue growth through the mid and late stages of the decade. Our appetite is really driven by what's gonna be a good strategic fit at the right price that returns to Lundbeck shareholders after we've paid for the asset. It's opportunistic as we go through. Within our strategy to profit from Lundbeck's significant experience in both neurology and psychiatry, all of those aspects are on the table.
We've also said that we'd like to be in high unmet medical need, where specialists are the driving prescribers, so that niche neurology, niche psychiatry, rare disease, neurology. Those are all the areas that remain in scope. I'm gonna ask Jacob to comment on the co-commercial opportunity for Alzheimer's agitation.
Thank you very much, Diana. We've never given guidance on these specific opportunities, but I would say the AAD would obviously be a good benefit to have on the label for Rexulti. If I were to rank it, also compared to what Deborah mentioned before, then the adjunct MDD is obviously the biggest indication and will be also the biggest, even if we had AAD on, but it's probably a bigger opportunity than PTSD. I would just caution that the physician overlap in terms of prescribing here is limited, so it also going to require additional efforts and cost to launch an indication in AAD, just so you're aware of that.
Johan, do you want to take on the 82422, which is the amlenetug?
Yeah. Thanks for asking that. I mean, first, generally phase two studies are, you know, by nature are proof of concept studies where we're finding out if things are working the way it should. The technical risk in this of course is lower because we're working with antibodies, so that's actually the benefit of both our phase two programs, that we're working with molecules that are very well designed to do their job. So we have a molecule that we're very confident is doing its job. The execution risk of course with MSA is a little challenging. It's a new indication for us. We are in the startup of the trial, just a few subjects in the trial, I have to say. It's quite a few U.S. sites that are now ticking up.
In terms of delivering the data, it's a little early to say timelines are really nailed down. It's still too early in the trial. In terms of the scientific risk, this is of course a high risk, high reward area. It's protein aggregation. It's in the realm of all those tau and amyloid antibodies that you've seen. But we have great confidence in this because we have quite supportive preclinical data, and we have also decent way of de-risking the trial forward. We are building this on biomarkers, where we're going to look at neurofilament light early on. So if there is not a promising sign, we can step out early, but with a promising sign, we can really invest and ramp up also substantially. It's different from Parkinson, I like to emphasize. This is a more rapidly progressing disease, more aggressive.
That is of course bad for patients, but it gives a little bit better chance of detecting a clinical signal. We have also other biomarker opportunities coming into this field. It's very rapidly moving. It's as good as you can talk about a phase 2 really at this stage in this area.
Great. Thank you very much. Thank you. Your next question is from James D. Gordon from JPMorgan. Your line is now open, James. Please go ahead.
James D. Gordon from JP Morgan. Thanks for taking the questions. Yeah, three questions, please. First one was just about migraine market dynamics and competition, and I know we had a question about slides already. My question would be can you see anything that can accelerate the uptake of injectables versus orals or make you gain a lot more share within the injectables? And I know that it's potentially true that the Vyepti is the more efficacious or the most efficacious option, but would you actually consider running a trial to show that's the case, so you'd have a stronger marketing claim? Or is there anything else that can mean you start making more share gains?
Second question, Rexulti AA, just your latest confidence and success at this final readout based on all the stuff you've seen so far, and we know it didn't work at the interim. Is there a scenario where you are statistically significant but it's not highly clinically meaningful or is the power in such that if you go over the line on the stat that it's definitely shown a very clinically meaningful benefit? Lastly, M&A plans, the shareholder vote on the share split next month, if approved, it would make it easier to do an equity-funded deal. Would you actually consider an equity-funded deal with Lundbeck equity trading where it is right now?
Okay, well, maybe I'll start with the last one. On the share split, we anticipate the general meeting in June, and it puts a tool in the toolbox. What we said from the get-go is we didn't have anything on the table that we were looking to use equity for. It is done with a long-term perspective in mind, and we also said that we would prefer that the equity was appropriately valued at the time we used it. We'll just reiterate those same remarks today. Jakob, would you like to comment on the market dynamics?
Yeah. No, I'll be happy to. I think it's important also to look at the total market and not only the injectables. The situation that we have now is a very competitive market, as we talked about, and that also means that the orals have taken their shares, sometimes blurring the line between what is episodic and chronic and also what is acute and prevention. That has given a lot more sort of treatment options to physicians and patients in the field. You've seen the orals come in and taking a larger market share that has impacted the injectables in a negative direction. You have a very competitive situation with a lot of different players.
For us, I think it's very important that we differentiate and we have a strong positioning in the market. We are focused on more severely impacted patients that are looking also or perhaps are on their way to develop, for instance, medication overuse headache or are experienced medication overuse headache, where Vyepti is the only product on the market that has those kind of data in its label. We have a unique positioning of a very efficacious product. That also means that it's not uncommon that you'll see some of the other treatments being used before you get to Vyepti. That's actually okay because we will offer a product that offers very significant efficacy and relief for patient.
I think the dynamic that you will see going forward is a very competitive market, a lot of sampling, a lot of sales forces that are impacting the market dynamics, and it will probably take some time before you have sort of that washed out. Then you'll begin to see a more stabilized situation where the different product profiles will gain the traction that they're supposed to have.
Great. Johan, would you like to comment on the clinical trial?
Yeah.
-dynamics-
I think.
the statistically significant versus clinically meaningful on the AA?
Yes. Let's start with I think you asked about the eventual head-to-head trials against various CGRPs. You may be aware that there is one reasonable one going on right now. Lilly started a Nurtec versus Aimovig trial. I'd like to point out a few things here. First, if that trial is showing some superiority or strong effect Aimovig versus Nurtec, that's of course very encouraging because we have, if anything, even a stronger and more powerful agent. We have not yet contemplated starting a phase face-to-face study against any of the others, but that's obviously something we could do. It is powerful and strong drug. We're not afraid of that. But we also, as Jakob pointed out, playing a slightly different space. We're working with the chronic, really hard patients.
While the other ones are blurring the picture, as Jacob said, they are more in the acute episodic, and episodic is not really that distinct indication. We're going for really the harder cases. In that space, we could definitely do something eventually to see how they perform each against each other. The question is, would that be against another mAb or it depends, and I think it would probably be against QULIPTA or Nurtec in that case. The question about agitation Alzheimer's, yes. The simple answer is significant on this CMAI scale is meaning clinical meaningfulness. Obviously, this is a scale that has not been used for years and years very extensively. It's considered a validated scale for the purpose, but you can always have conversations with the regulators, what is clinical meaningful on a scale?
From our perspective and with the past conversations we had, and remember, this is a long program we had with two previous phase III trials, we have pretty good understanding what it takes to also hit on clinical meaningfulness. That's what we're aiming for with the readout.
It's basically significance is the same as clinical meaningfulness here.
Next question.
Your next question is from Keyur Parekh from Goldman Sachs. Your line is now open, Keyur. Please go ahead.
Thank you very much. Two separate lines of questions please. First, coming back to Vyepti. Hi. Sorry, can you hear me?
Kayur.
Yes, please go ahead.
Okay. So just on Vyepti. I'm conscious of the messaging around the increased deductibles in the first quarter from a U.S. perspective, but would appreciate any incremental color you might be able to give what the underlying growth rate was without kind of those deductibles, both kind of either on a U.S. basis or on a global basis. Secondly, as you look at the full year numbers for consensus for Vyepti, it is close to DKK 1.2 billion. How comfortable are you that consensus is modeling this correctly, given the first quarter trends? That's kind of on Vyepti. Then secondly, Deborah, coming back to the questions around kind of M&A and kind of transactions, et cetera.
At the time of the original announcement, you said kind of you weren't looking at anything in the near term that it was more to create optionality, which you have kind of reiterated today. As you look at the correction in the pricing for biotech assets over the course of this year, does it put you in a more interested frame of mind to pursue something sooner rather than you might have otherwise done? If not, why so? Thank you.
Great. Jakob on the deductibles.
Yeah. Thanks. I think we also mentioned it at the conference call the last time that you're absolutely right. There hasn't been an impact on deductible reset and also reauthorization of insurance in the first quarter. We haven't quantified that, meaning what that exactly means. I think when we look out for the full year, which makes it difficult, but I don't think we're giving guidance. If I look at consensus, then I would say that I'm comfortable. Please do remember that also when we're looking into a very competitive market that we have traction with Vyepti, especially in the chronic segment. We have growth in our market share there. We also see the persistence and usage of Vyepti is growing.
We have just launched a patient activation campaign in the U.S. that we're trialing. Those factors mean that we do expect to see continued growth of Vyepti. It also means that some of these factors may be coming in a little later in the year than right now at this quarter. Without saying too much about how we end the year, I think that's probably the closest I can get at this time point.
I think the U.S. market is the only market where we see this resetting.
Yes
... of deductibles and insurance reauthorization. The other markets, obviously we're just coming into the negotiation, but of reimbursement in Europe. Once that's done, patients don't have to reauthorize. To your questions on M&A, there has been a reset in the market for sure, and some companies are much more affected than others. The ones that are carrying a relatively heavy R&D burn and have some time till their readouts tend to be the most affected, right? Those are the prices that have come down the most. What we've been saying is, if we were doing M&A, it'd probably be more towards the near term accretive.
That we're not doing M&A in the mid-stage pipeline right at this moment because we want to first get through the investment period in the globalization of Vyepti, that has us at a pretty high R&D burn. Some of those other companies, there's been a bit of a downdraft, but they haven't reset quite as much. We keep looking at where is the value, what is the value to our business, and we'll act at the time that we see the alignment of the strategic fit and the appropriate valuation. I wish it were yesterday, but, you know, we'll just be looking forward to the time that those things come into alignment.
Thank you, Deborah. Could I just perhaps clarify a comment you made earlier in reference to the Vyepti answer? Should we be thinking of this as maybe a second half kind of pickup in trends and not necessarily a second quarter pickup in trends? Is that kind of a fair implication of your comments?
Yeah, it is. I think, yeah, let's leave it at that. Yes.
Thank you.
Thank you. Your next question is from Marc Goodman, from Leerink Partners. Your line is now open, Marc. Please go ahead.
Just to continue on with this Vyepti, can you talk about maybe the numbers of patients that have been on the product in the United States, and what types of patients are you getting? Are these naive patients or are these mostly patients who've tried the orals or other injectables or maybe can give us a sense of that. Back to the comment about the gross margin, maybe if you give us an idea of how we should be thinking about the gross margin the rest of the year. But also, you know, maybe the next couple of years just given these changes that you were mentioning with some of the royalties and amortization changes and stuff like that. Thank you.
Great. Bjørn will take the gross margin question. Jacob, you dive in on Vyepti.
Yes. I can give you a little perspective here. I think it's fair to say also with the patient positioning the brand strategy that we have, that we are, I think Johan also used the word, looking and targeting Vyepti towards patients that, are more severely impacted patients. That naturally means that many of these patients have tried many different medications, before they get to Vyepti. It's not uncommon that they may also have tried an oral gepant. In that flow, that is actually what you should expect, that they have tried, something else before Vyepti. The most of our patients are in that severe segment, of, high-frequency episodic patients or, the chronic patient segment.
That's actually also where we see a lot of benefit and positioning of the brand.
Yeah. I think that we see Vyepti delivering for those patients. Regardless of whether they've come off older therapies like the topiramate, whether they've had one or even two injectable CGRPs or again, anecdotal data, people coming off orals for whatever reason, lack of efficacy or tolerability, we do see them responding to Vyepti. It's a great place that migraine patients now have a number of opportunities, but there is a lot still remaining that don't get benefit from all of those other therapies and that are still getting benefit from Vyepti. Bjørn, would you like to?
Can you give us a sense of how many patients have been on the product?
I don't think we've given out that number, and so, I will also refrain from doing that today.
Yeah. The question on the gross profit, we expect to stay at the level we have shown. We don't see significant changes in the business to that, so we still expect in the level of around 78%-80%, also going forward.
Report it.
Report it.
Hello, Marc. Any more follow-up questions?
No, no. Thank you.
Thank you. Your next question is from Jo Walton, who's from Credit Suisse. Your line is now open, Jo. Please go ahead.
Thank you. Three quick ones. Just to follow up to James' question on the clinical utility in agitation. Could you just give us some idea of what you mean by clinical utility? Is it all the patients who were, I don't know, agitated for six hours a day and now agitated for four hours a day, so that's clinically meaningful, but hey, the patients are still agitated? Or we're just trying to get a sense of the you know, the speed of pickup by the degree of clinical utility that you could get from, say, a four point reduction in the CMAI scale. My second question is just on the overlap of doctors. So at particularly outside of the US, are the same doctors prescribing migraine drugs as they're prescribing some of your other drugs?
Just trying to think of the level of incremental marketing that you may have to put behind this, particularly as you've said that Biohaven is aggressive in the US, and presumably Pfizer is equally aggressive ex the U.S. Finally, just one, and I'm sure I should know the answer to this. You say that you're doing very well with Trintellix in China without it being on the NRDL. Do you have a possibility of getting on the NRDL, and if so, when? Thank you.
Okay. Johan, would you like to comment on the Alzheimer's agitation utility?
Yeah. Let's start. First of all, the SIMI scale is a composite scale with several items that we put together, and it's given at one time point a day. We're not getting the resolution or the 24-hour time point. This is a visit to the doctor and you give the scale at that time point, and it's we try to keep that at a certain time of the day. We don't have that resolution how quickly it works. This is for chronic therapy. Obviously it could be interesting to see if it sets in quickly, but as with most neuroleptics, you expect that it takes a little while before the effect kicks in. That's not usually the key event here. The key event is to see a more chronic improvement.
The scale has many, many sub items, and we look at all the different sub items. We have a little special, sort of balance in the scale how we look at this. In terms of clinical meaningfulness, utility, that is really the way it's considered. If you have a certain degree or points on the composite scale, overall combined composite scale, you are considered to be clinical meaningful. As I emphasized before, this is of course a discussion one needs to have with the regulators because the scales are not at that validation level, so they're being used extensively. It's not an ADAS-Cog or CDR Sum of Boxes or anything like that. This is a slightly newer scale.
I'm sure there could be some discussion about the clinical meaningfulness, not really utility, because in the question of utility, I heard your time points, and I hope I answered your question properly.
Great. Thank you.
I wasn't thinking of necessarily the speed of action, but I think you've answered it. It's, let's say, 3:00 P.M. that every time you do the measure. I was just thinking in an institutional setting, which is presumably where you'd expect the fastest ramp up, and this is where you know, Alzheimer's patients are just sort of routinely given off-label drugs. It was just whether you had a sense that this would make people just easier to manage at certain times in the day, or just some people not have the agitation at all and therefore be able to you know, function on their own to a greater level. We'll just have to wait and see the data, I guess.
Yeah, we need to see the data. Just to remind you, we have about 50/50 outpatients in home care of various kinds and institutionalized patients. We're going to have a look at both sort of categories here. I show the data that majority of patients with agitation probably are in home care, and this is a major factor to go into nursing home. It's very important to actually delay that, and that is the rub with the old neuroleptics. They have all these side effects that make them a little hard to use in an outpatient setting. That's where we think Rexulti could have a good place because it has clearly a better tolerability profile than other neuroleptics that are used now. It's kind of a slightly different take on this.
You like to delay people to go to the institutions. In institutional care, obviously, the good old way is to basically sedate the patients. You like to have a calm nursing ward. That is not the idea here. We like to treat the symptoms.
Great. Moving on, Jacob.
Vyepti and the short answer is there is not an overlap to our existing sales force. It is incremental what we are building for Vyepti when it comes to sales force to launch Vyepti, and that's also why you will see increased cost as we are rolling it out globally. That being said, remember that this is a specialized product and in many places it will be hospital, some places, headache clinics that will administer Vyepti or infusion centers. It is a more targeted group of physicians that we're going to see with the Vyepti around the world. NRDL for China, Brintellix, absolutely correct. We don't have NRDL.
We've been negotiating with the Chinese regulators around this a few times, but haven't been able to reach an agreement on price. For now, we don't plan to have NRDL for Brintellix.
Thank you very much.
Thank you. There are currently no more questions in queue. I'd like to hand the call back over to our speakers today for their closing remarks. Speakers, please go ahead.
Thanks everyone for joining us today. We're very pleased with the outcome of our first quarter, and we look forward to continued growth and momentum in the coming quarters ahead. Enjoy your day.