Good morning, everybody, and thanks once again for joining us at the 45th Annual TD Cowen Healthcare Conference. I'm your own Yaron Werber from the Biotech team, and it's a great pleasure to moderate the next Fireside Chat with Amgen. To my left is Jay Bradner, Executive Vice President and Head of R&D. I think this is officially our first Fireside Chat together.
Yes, it is.
And to his left is Justin Claeys. I need an introduction, VP of IR. Justin, this is not our first Fireside Chat together.
Nor less.
So let me turn it over to Justin and then Jay to make some opening remarks, and we'll go into Q&A.
Great. Good morning, everyone. Thank you for hosting us, and thank you, everyone, for joining us. It's an exciting time for Amgen, and we're glad to discuss the opportunities ahead. We exited 2024 with strong momentum, including 10 products growing at double-digit sales rate, 14 products annualizing at over $1 billion in the fourth quarter, and 21 products delivering record sales for the year. This momentum supports our growth outlook for 2025 and through the long term. The breadth and depth of our portfolio spans our four therapeutic areas. Let me highlight a few key drivers in each. Starting with general medicine, Repatha is now a multi-billion dollar product with 36% year-over-year sales growth in 2024. Cardiovascular disease remains the leading cause of mortality worldwide, and we see continued robust growth for Repatha, especially with strong access in place and price stabilizing in 2025.
This opportunity could be further augmented with a second-half readout of our phase III primary prevention trial, VESALIUS-CV. Our bone builder Evenity also delivered in 2024, with sales increasing 35% year-over-year. Despite its strong growth trajectory, the large majority of patients at high risk for fracture from postmenopausal osteoporosis remain untreated, highlighting the continued opportunity for expansion. Turning to the general medicine pipeline, we are excited about MariTide and look forward to sharing more detailed results from the first 52 weeks of our phase II study at the upcoming ADA meeting in June. We also look forward to sharing results from the second 52 weeks of this phase II study later in the year. And of course, in cardiovascular, our phase III outcome study of Olpasiran in individuals with elevated Lp(a) is fully enrolled and continues to progress.
Turning to rare disease, this portfolio has four products early in their life cycle with significant growth ahead, building on $4.5 billion of sales with 17% year-over-year growth in 2024. Starting with Tepezza, we continue to execute on the low Clinical Activity Score opportunity in the US while launching and gaining new approvals internationally. It's a landmark year for Uplizna with two anticipated approvals on the horizon, namely an IgG4-related disease with an April 3rd PDUFA date and a generalized myasthenia gravis where Uplizna has been granted orphan drug designation. In inflammation, Tezspire continues its strong ramp in severe asthma with sales up 71% year-over-year in 2024. We are advancing Tezspire in additional indications highlighted by COPD, the world's third leading cause of death, where we plan to initiate phase III studies in the first half of 2025.
We also recently shared compelling phase III data in chronic rhinosinusitis with nasal polyps, which was also published in the New England Journal of Medicine. Our innovative oncology portfolio is well positioned for continued growth, including our bispecific T-cell engager platform. Blincyto is moving into earlier treatment lines, demonstrating compelling survival benefits in B-ALL. Imdelltra is showing impressive potential in small cell lung cancer, and Xaluritamig is advancing in prostate cancer, adding another promising program to our late-stage innovative oncology pipeline. In precision oncology, we look forward to two phase III readouts for Bemarituzumab in 2025. Our biosimilars continue to be an important contributor to our business, with sales up 60% year-over-year to $2.2 billion in 2024. We launched Pavblu at the end of last year and Wezlana in the U.S. in January, and we expect to launch Bekemv in the U.S. in the second quarter.
Given our strong biosimilar performance in the market and our pipeline of new biosimilars, we remain on track to more than double sales from 2021 levels to over $4 billion by 2030. Given that we're already in March, let me remind everyone of a few points from our fourth quarter earnings call on the outlook for the first quarter. First, we provided guidance that we expect first quarter non-GAAP operating margin as a percentage of product sales to be around 42% and to accelerate in subsequent quarters for a full year average of 46%. This includes a typical pattern of lower sales in the first quarter for certain products, including Tepezza, Enbrel, and Otezla. Also, we provided guidance that we expect relatively consistent revenue growth for each quarter of 2025.
In other words, whatever growth rate you were assuming for the full year would be roughly the same across each of the four quarters. Peter provided commentary on additional items for the first quarter and the full year, and I'd encourage you to reference the Q4 transcript for those. In summary, we have momentum across the business and are focused on strong execution for our in-market products, our rapidly advancing pipeline, and biosimilars. Jay, let me turn it over to you now for a few comments.
Yeah, thanks, Justin. And, Yaron, it's great to be here with you, and thanks for the invitation. We have some exciting news to share this morning that our progression of the MariTide obesity medicine is progressing quite well. And this year, we intend to initiate a number of phase III clinical trials across both obesity and chronic weight management, as well as a number of obesity-related conditions. Pleased to share with you all this morning for very much the first time that we've now initiated both of the phase III studies. Soon to post to ClinicalTrials.gov are some of the high-level descriptors for this trial, and I'm happy to share some insights into that here this morning. There are two phase III clinical trials both initiated. One will be in patients with obesity or overweight without type 2 diabetes.
We anticipate enrolling 3,500 patients on that trial. The second is for patients with obesity or overweight who have type 2 diabetes. We intend to initiate 999 patients on that trial. The primary endpoint will be a change from baseline body weight at 72 weeks, and our approach to dosing, we'll have a chance to describe in the fullness of time, but for today, you can think of it as three doses: high, medium, and low, and you could think of a titration scheme as starting lower, but we're delighted to share that these trials have now been initiated, and really the progression of the MariTide phase III program is going very, very well.
Wow. Okay, that's big news. So I was going to leave MariTide for a little later, but I think we're going to move it. Let's move it up. So this is going to be the data so far has been really interesting, and you've shared a little bit of the phase I healthy volunteer data that I think you're probably referring to starting low. Although, just to remind the audience, in the phase II, you also had a starting lower in the phase I healthy volunteers, you really started low, right? And you escalated up, and you either escalated up over a month or over three months. Can you give us maybe a little bit of a hint? Is it one of those schemes, either one month or three months titration?
Today I won't provide discrete insights into the dosing approach for phase III. MariTide has proven itself highly efficacious, also very well tolerated with antecedent low-dose escalation. This can come as no surprise because the entire class of GLP-1 targeting medicines requires lower dose dose escalation. As you kindly referred, our phase II study, which had 11 arms, featured only two arms sampling dose escalation. We undertook to perform concurrently a phase I pharmacokinetic study that could provide really discrete information around drug exposure, as well as give us experience with two additional dose escalation schemes.
From these two sets of data that we've largely presented in our last engagement and teleconference, but we hope to and expect to present even more data at the ADA meeting mid-year, we have all the guidance needed to, we believe, to undertake phase III clinical investigation across a number of indications with a dose escalation approach that will provide a terrific patient experience. I would remind that with dose escalation, we observed a very low discontinuation rate overall of 11%, 8% or lower due to GI effects. We had outstanding persistence across the study. And in fact, as you probably remember, this phase II study was designed to feature a second calendar year that patients were invited to continue participating in this study so that we could understand maintenance dosing and lower doses. Indeed, 90% of patients eligible chose to take another year of MariTide.
We take all of this as a strong vote of confidence that emerging from phase III will have a very competitive tolerability profile, and what's more important, a great onboarding patient experience so the patients can take this medicine and benefit from it for a long, long time.
In the phase I healthy volunteer, that was a 43-day dosing scheme, right? Maybe just correct us, just remind us, how do you dose escalated and how long did you follow for efficacy?
What we presented was the interim analysis from a three-arm phase I pharmacokinetic study where we sampled one of the dosing schemes that we had prior experience with from the phase II. This is to help with almost an apples-to-apples comparison. There are major differences in how one undertakes a phase I study with sample collection and intensive clinician interaction over a very short period of time versus a study like a phase II that's more like how one might be managed on the Serengeti of medical practice. And so we wanted to emulate discreetly one of the dose escalation experiences from phase II. That proved to be very helpful. The other two dose escalation schemes had lower index starting doses of 21 or 35 milligrams. This gave us a very good experience with that first dose of MariTide and what associated symptoms we might observe.
In the interim analysis, we did not as yet have the full data from either the pharmacokinetics or a longer-term follow-up. Longer-term follow-up isn't even the right term for a phase I study. But we did have a snapshot of the data, an informative snapshot of the data, and felt that it was adequate to present our experience. With lower dose escalation, we were able to, just in that study with two additional dose escalation schemes, achieve an onboarding of MariTide that had an increasingly competitive profile with approximately 20% or lower incidence emesis.
So it was less than 20%, so I think it was dramatically lower than it was previously.
Yes, it depends how you define drama, but it was meaningfully lower.
Dramatically.
Yes, yes.
Yeah.
It was a step in the right direction. From phase I to phase II, we learned a lot, and we saw a very meaningful decrease in incidence nausea and vomiting. From phase II to phase I with this PK study, we cut that number almost in half. So the trajectory of informative data gave us a very strong learning going into phase III. I also want to point out that we talk about these absolute numbers and their incidence numbers, and it's very important, very important. I would also point out that these symptoms were very mild. They were very transient. As we shared in that Manhattan plot at our more detailed teleconference, they're quite limited to just the early experience with MariTide. Across the whole of the ensuing 52 weeks, patients received this medicine monthly on that trial without incident.
In the 72-week study, are they getting monthly doses after the titration throughout the 72 weeks, or is there a chance to switch at 52 weeks from monthly to less frequent?
Are we talking about the phase III studies that we just initiated?
Phase III.
Yes. We'll have more to share about the design of those trials and the fullness of time, but they've strongly benefited from our experience to date with the medicine.
Do both studies have the same three doses?
Both studies will feature the same three doses.
Randomized one-to-one-to-one against placebo?
It is a randomized controlled trial of low, medium, and high-dose MariTide.
Is the titration the same, at least day 0, 14, 28, and then or?
Both studies employ the same dosing scheme.
Okay. So with TBD, exactly how you dose escalating?
Correct, yes.
You're just waiting to put that on clinicaltrials.gov?
ClinicalTrials.gov should go live really at any time now that we've initiated this study. We really want it up online to encourage patients to enroll and participate.
What formulation are you using? Is this the commercial formulation? Is this an auto injector?
We haven't gone into those details publicly. It is very important that one studies the material and ultimately the format with which you go to market, and we'll have more details on that in the fullness of time.
Okay. But there could be three doses in that study, but those are the doses after the escalation. So I imagine you have an escalation, and then you have three different doses.
That's right. We will escalate to target doses of low, medium, and high, and I hate to be so opaque. It's just, it's a competitive space, and we're very excited about these studies and actually can't wait to share more details, but at the right time.
Yeah. Maybe just give us a little bit of a sense that the choice to use a 72-week endpoint in this study? There's been endpoints at different time points for different.
Yeah, happy to give some insight there. First of all, it's quite standard among these trials. And secondly, as we were excited to share when we reported the early returns from part one of our phase II study, that one of the remarkable findings of that trial was that we observed 20% weight loss, approximately 20% weight loss in patients with obesity or overweight without type 2 diabetes, and 17% approximate weight loss in patients with obesity or overweight with type 2 diabetes. And these are strong numbers. And we observed the data, which we shared in graphical form. You could view it yourselves. The absolute magnitude of contribution had yet to achieve a plateau. And so seeing these data not as yet level out made us very motivated to characterize a longer-term experience to really understand the capacity for real benefit for patients with obesity and overweight.
It is just true that incremental weight loss, even over 20%, can confer significant medical benefit, and so we designed our phase III trials in this way.
Yeah. And then the data at ADA, what can we expect? Is it going to be the obesity data and some data from the diabetes study, and how much follow-up would there be?
I would expect at the ADA, I mean, we've already presented a lot of data. That teleconference that we held has more data than most podium presentations, but we wanted to give the community a clear sense of the characterization of the medicine to date. I would expect the ADA presentation to go to even more detail around that phase II data set, which is so rich. I mean, 11 arms of data.
Yeah. If anybody has any questions, feel free to raise your hand. We just need to get a mic. Why don't you go ahead and we'll repeat the question here.
Obviously, the elephant in the room that everyone wants to know about is the interval. Is there anything you can say on the interval at this point, whether one month, three months?
Oh, I see the schedule, the dose schedule. No, not at this time. We have a clinical experience now with monthly dosing, with every other month dosing, and in part two of the phase II study with every three-month dosing. And this is the advantage of working with a medicine that has an immunoglobulin core backbone, is that patients can experience very steady, very stable, and predictable pharmacokinetic exposure as opposed to the jigsaw of weekly subcutaneous injectables. And so we've been very motivated to characterize that pharmacology at each of those three-dose schedules, and we'll have a chance to share our phase III designs later.
Yeah, Jay, congrats on MariTide.
Thank you.
When you started on this journey, demand was probably less well-known, but pricing was probably viewed better. It's kind of flipped now. How do you see the pricing environment?
Justin, I'd love to get your insights here.
Yeah, I think it's probably a bit early for us to comment on pricing and where it's going. I think what we would highlight is that this is a huge unmet need, that the demand is tremendous. There's different figures around the epidemiology, but you hear upwards of a billion people worldwide reflected with this. We also think that there's going to be, it's a heterogeneous situation. There's going to be different medicines and treatments required for different patients. So we feel like there's going to be plenty of room for MariTide, and it'll be a good opportunity. The unmet need is just not met, which is crazy, right? Because there are these incredible paradigm-changing medicines out there, yet real-world data as published by others, one calendar year, 65% of people are no longer taking weekly subcutaneous injectable obesity medicines.
And so given the massive burden of this disease and its prevalence, especially in this country, and the apparent feedback from patients, prescribers, in real clinical practice, we think there's still a remaining huge unmet need. These are all chronic conditions that we're studying, that we're all studying: obesity and overweight with all of its comorbidities, and then discretely, heart failure, atherosclerotic cardiovascular disease, chronic kidney disease, obstructive sleep apnea, MASH. Those diseases are not optimally treated with a medicine or an approach that only 35% of people can stay on a drug for a year off a clinical trial. And so we think that there's a significant residual unmet need, and that prescribers, patients, and payers will recognize this.
So I'm going to maybe ask a quick question on manufacturing, but before that, I'm going to shamelessly put in a plug that we published last Thursday, and you can actually see it, and we apologize if I'm in the area of saying it over and over again, a video with Amgen and Generate:Biomedicines focusing on how Amgen and Generate:Biomedicines also, and their partnership, and Amgen extensively is using AI, anything from drug discovery to their packaging plant, and you can actually see the New Albany, Ohio plant in that video that is currently already doing Repatha. I think some Prolia is already getting packaged there, and I think that plant, you've said publicly, will eventually handle all future biologics too. There's a lot of expansion capacity in that site, but that's a packaging plant.
North Carolina is your new biologics plant that I think is supposed to open next year. Is that correct? Maybe say whatever you can about that. And then secondly, have you broken ground on the extension yet?
Sure, yeah. So thanks for the opportunity to comment on it. Maybe just stepping back one click, I've had the pleasure to be with the company for a number of years, and I think what's probably not totally appreciated from the outside is how the deep expertise, the commitment to manufacturing excellence that the company has. There's a mantra within Amgen, every patient, every time. There's really a badge of honor that the team works so hard to make sure that all of our medicines reach the patients who need them. So it runs deep throughout the company, and I think the investments we're making in Ohio and North Carolina really exemplify that. In terms of North Carolina, what we've shared is that it's a high-yield drug substance facility. The first portion of that investment was announced, and that's expected to be approved by the FDA in 2026.
So you're right, Yaron, that'll be next year. We subsequently announced an additional $1 billion of investment in the site. And as you know, the site will support a number of products. Obviously, MariTide is a driver, but actually, it's certainly not just MariTide. We have volume growth going across the business. So in total, our investment in that site is over $1.5 billion. In terms of the second leg of the investment, we had a ribbon cutting earlier this year. We're looking forward to breaking ground and rapidly advancing that one. So full steam ahead there.
So that's going to be a second facility.
Or second, maybe a second portion of the site.
Of the site,
yeah. Okay, I'm going to move on. There's so much to talk about. I think that then I'm going to maybe shift the order a little bit here. So maybe we'll focus on Rocatinlimab next because we're expecting two additional sets of data. Maybe just a broad question. The HORIZON study, I think we're going to see the full study at some point. You tested lower and mid doses relative to what you tested previously. Just remind us there was a loading dose in that study too. Your dosing is, and that was a Q4 weeks. And well, in the phase IIB, you tested Q4 and Q2 weeks. So I guess my question is, what can you share with us on dosing for HORIZON versus what we're going to see from the upcoming studies, which I believe the SHUTTLE and the VOYAGER studies are coming soon?
IGNITE. Rocatinlimab is an OX40 targeting monoclonal antibody. We're developing this medicine in atopic diseases and extensively in atopic dermatitis. Atopic dermatitis, we've undertaken a program called ROCKET that is eight phase III clinical trials building on very exciting phase II clinical trial data. This is a first-in-class, first-in-mechanism medicine that rebalances the T-cell compartment. OX40 is a signaling pathway that drives inflammation in this and other diseases like prurigo nodularis et al. But importantly, by targeting the receptor of OX40 with a depleting strategy, we don't only impair signaling of OX40 to these inflammatory tissues, we remove OX40 positive autoreactive T-cells without impairing the healthy T-cell compartment, which is very important from a tolerability standpoint. And there's, in that way, no medicine like it in development for atopic dermatitis today.
Building on the very strong phase II data, we undertook these eight phase III clinical trials that will importantly characterize rocatinlimab in a half-year dosing exposure as well as a longer-term extension in adult patients and in adolescent patients with and without the allowed use of corticosteroids applied topically and with a maintenance dosing schedule. We have experience with Q2, Q4, and also within the larger program, Q8 week dosing. And with the aggregate data reading out by the end of this year, we have three studies still to read out this calendar year. We'll have a good sense of the target product profile as well as the intended approach for treating patients in the marketplace.
So how do you, you know, when we do a lot of these panels and physicians consistently like the Sanofi approach better so far, at least that's the view out there a little bit and I think it's been a function of maybe their previous data. There's an appreciation or thought that it offers more potency, slightly better safety, but also they're testing Q12 week doses. Your data looked fairly durable just like they did in the phase IIB so why only do Q8 weeks and then thoughts about kind of where do you fit in the paradigm?
It would be reasonable in the fullness of time to explore longer interval dosing, especially in the maintenance paradigm. The depleting strategy for T-cells could have scientifically a much more durable impact. I mean, look at the experience of depleting B-cells and the durability afforded with medicines like Uplizna in autoimmune or inflammatory diseases. Guided by the pharmacology as well as the phase II efficacy data, we feel great about a Q4 week dosing schedule and are interested to, at the right time, share when we have the full data, the Q8 experience. Regarding the comparisons, it's very hard, especially with medicines that have yet to read out their full phase III data sets.
But I would highlight again that mechanistically, though these both build off OX40 pathway modulation, it's quite a different thing to the immune system to take out just a single ligand and block its signaling versus to deplete autoreactive T-cells.
You would think that depleting the autoreactive T-cells will give you a more durable effect.
I mean, you know, we approach these studies with equipoise. We're surely hoping that both the proportion of meaningful responses and their durability could be better, but these will be limited by the inability of comparing between clinical trials.
Does it make sense to push the dose maybe higher?
We have a very strong dose ranging experience with Rocatinlimab, and I've not as yet seen any data to suggest that we need to approach doses higher than those that we are including as the high doses in our phase III ROCKET program.
I want to maybe move to Uplizna and specifically in GMG. The phase III data, the main study was presented at MGFA, that was the 26 weeks. That study is still blinded, reading out the 52-week, I think presumably this year. Do you need that 52-week data to file, or can you file with the 26-week data?
We should not need that 52-week data to file. There's no limitation on our capacity to file from the data we already have and are approaching a registration strategy full force. The Uplizna data in generalized myasthenia gravis is quite strong. And at the time that we read out the 26-week data, the numbers were continuing to improve. And so Justin are very excited to see and to then share the 52-week MG data with Uplizna.
I mean, I think you're talking about filing in the first half, and you had for GMG, or?
Yeah, we haven't specified yet.
You just said filing in this year.
Yeah, exactly.
Filing this year, so you had the data for MGFA, presumably you probably even had the data a little bit earlier than that, so 26, another 26 weeks is probably going to read out soon, so theoretically, you could actually ultimately have that 52-week data at the time in which you file. The Wall Street always loves to look at the MGADL differences and immediately do math, and we totally get it. When you talk to physicians, they actually think this profile is super compelling, zero, 15 days, and then essentially Q6 months, it was very well tolerated. MG-ADL, as you said, continues to, the curves are diverging, so that 52-week durability is going to be critical, and they actually think this mechanism could be used a lot more broadly. I think Wall Street right now is thinking it's going to go more niche.
Thoughts about what I just said?
I mean, it really resonates with me, to be honest with you. Just objectively, moving the MG-ADL clinical score, which is also used clinically to follow patients in the real world, by 4.2 points compared to a placebo of 2.2 is really quite meaningful. And to do this with a medicine that has a loading dose and then from there on can be given on a Q6 month schedule is wonderful for patients, especially those that are responding that don't want to feel like a patient taking a medicine every couple of weeks or worrying that they're going to miss their medicine and it flares right back up.
And so here, the durability of CD19 B-cell depletion, which is not just the mature B-cells, but also some of the more immature cells that can really drop these autoantibodies and has dropped these autoantibodies meaningfully, we think is a very strong offering. And I'm sorry, you're wrong, I'm going to correct myself. We did say we were going to file in the first half. We haven't specified the approval date, so just wanted to correct myself.
Okay, okay.
It was shown that at J.P. Morgan.
Yeah, that's right. The onset with Uplizna is shorter than, let's say, C5 or an FcRn. But as you said, you also showed the ability to taper steroids at the same time. What's an ideal patient that can go on Uplizna as opposed to going on an FcRn, let's say, or a C5?
What's the profile of the patient?
Or kind of ideally, where do you think this ultimately gets used kind of in the first year and three years out?
I think it gets used in people sick with generalized myasthenia gravis who don't want to be taking steroids and seek to have a highly efficacious, durable medicine that they can take every six months and not worry about their disease. FcRn medicines are quite active across a broad number of autoimmune conditions. They have different issues with some advantages, such as the immediate onset of action, some limitations, such as the high target mediated drug disposition and the very rapid turnover of the pharmacologic agent that requires constant dosing, and so I think it'll be different horses for different courses for the patients, but those that seek a strong and durable benefit with every six-month dosing will be right for Uplizna.
And I know we're at time, but Justin, maybe one quick question for you. Any update on Pavblu's launch?
Just to reiterate what we said on the earnings call, we're pleased with the launch so far. We disclosed that we recorded $31 million of sales in the first nine weeks. The team is fully deployed, talking to customers, and we're getting good feedback on the presentation, both the prefilled syringe and the vial. So I think so far, so good.
Okay. Well, terrific. Jay, Justin, thanks so much for joining us. We appreciate it.
Thank you.
Congratulations.
Appreciate it.
Thank you.