Amgen - Q4 2025

Transcript

Operator (participant)

My name is Julianne, and I will be your conference facilitator today for the Amgen Q4 2025 earnings conference call. All lines have been placed on mute to prevent any background noise. There will be a question-and-answer session at the conclusion of the last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press star, then the number one on your telephone keypad. To withdraw your question, please press star one again. I would now like to introduce Casey Capparelli, Vice President of Investor Relations. Mr. Capparelli, you may now begin.

Casey Capparelli (VP of Investor Relations)

Thank you, Julianne. Good afternoon, everyone, and welcome to our fourth quarter 2025 earnings call. Bob Bradway will lead the call today and be followed by a broader review of our performance by Jay Bradner, Murdo Gordon, and Peter Griffith. Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement, and please note that actual results can vary materially. Over to you, Bob.

Robert Bradway (CEO)

Okay. Thank you, Casey, and good afternoon, everyone. Thank you for joining us today. Today, we'll cover full-year results for 2025 and provide a preview of what to expect from us in 2026. Amgen delivered strong operational performance across the board in 2025, and you can see that in the breadth of our business. Note that 14 of our products achieved blockbuster status, with sales of $1 billion or more, 13 products delivered double-digit sales growth, and 18 products achieved record results for us. The strength of that broad portfolio enabled us to post double-digit growth in revenues and earnings per share for 2025. Looking to 2026, I would highlight six areas of momentum. Three of these, Repatha, Evenity, and Tezspire, all grew by more than 30% year-over-year in 2025. These medicines have a few important things in common.

First, they're highly effective, innovative therapies that address important public health needs. Second, they're leading products in their fields. And third, while each of these products represents a multi-billion dollar global franchise already, they address areas of large unmet medical need where there are millions of patients yet to be treated. In this sense, they represent growth drivers, not just for 2026, but for the rest of the decade. In rare disease, our portfolio generated more than $5 billion in sales in 2025. Here, too, many of our medicines are early in their life cycle and positioned as leaders in their respective categories. Growth has been fueled by reaching new patients, expanding into additional geographies, and launching new indications. We see further opportunity ahead as we scale these therapies. Uplizna exemplifies this growth opportunity with approvals in IgG4-related disease and generalized myasthenia gravis in 2025.

Our innovative oncology portfolio grew at 11% year-over-year in 2025, driven by our bi or bispecific T-cell engager medicines. We're particularly excited about Imdelltra, which has rapidly become the standard of care in patients with second-line or later small cell lung cancer, supported by unprecedented survival benefits. We're an industry leader in biosimilars. Our biosimilars portfolio has contributed more than $13 billion in sales since the launch of our first medicine there in 2018. With $3 billion in 2025 sales, this business is an important contributor to our organization and poised for growth with the next wave of biosimilar launches. You can appreciate the depth of our business through the lens of our research and development activities.

2026 will be a year of disciplined data generation from a number of exciting phase II and phase III programs that will pave the way for long-term growth at Amgen. Our confidence continues to build in MariTide as a differentiated treatment for obesity, type two diabetes, and obesity-related conditions. In a field featuring dozens of potential daily, oral, and weekly injectable medicines, MariTide stands alone as the only therapy in late-stage development to offer the paradigm-changing prospect of strong efficacy and favorable tolerability at monthly, every other month, or even quarterly dosing. In addition to MariTide, we remain excited about Olpasiran and what it might represent for patients with elevated Lp(a), a heritable risk factor for cardiovascular disease. We see Olpasiran as an opportunity to build on our leading positions in cardiometabolic disease.

It shouldn't be lost on any of us that Repatha, Olpasiran, and MariTide together would represent a very compelling set of cardiometabolic medicines to expand our leadership in the treatment of serious chronic diseases well into the next decade. Beyond the pipeline, there's a great deal of enthusiasm about the convergence of technology and life science, and based on what we're seeing at Amgen, we believe that enthusiasm for convergent innovation is well-placed and will have significant impact on how we discover, develop, and commercialize medicines. As always, I thank my Amgen colleagues around the world for supporting our mission to serve patients. With that, let me turn it over to Jay for an update in R&D.

James Bradner (EVP of Research and Development)

Thank you, Bob, and good afternoon, everyone. Fourth quarter capped off a year of strong, disciplined execution across R&D.

... Throughout 2025, we advanced multiple late-stage programs, delivered five-key regulatory approvals, and strengthened the evidence base supporting our marketed medicines. Taken together, these contributions demonstrate real scientific rigor and illustrate the breadth of opportunity ahead. Let me begin with MariTide, which continues to develop in meaningful and very encouraging ways. The MariTide phase III program is rapidly advancing, with strong enthusiasm from investigators and participants. Both of our phase III chronic weight management studies are fully enrolled, and our ASCVD and heart failure outcome studies are progressing well. In parallel, we continue to expand the clinical landscape of MariTide across obesity-related conditions as we begin enrollment of our two phase III sleep apnea studies in adults with and without positive airway pressure therapy. Altogether, we now have six global phase III studies underway with MariTide, collectively designed to deliver a comprehensive evidence base.

In addition, as we shared last month, we've completed part two of the MariTide phase II chronic weight management study. We also completed the first 24 weeks of the phase II type II diabetes study that enrolled participants with and without obesity. Results from these two studies further increase our confidence that MariTide can represent a new paradigm in obesity, type II diabetes, and other obesity-related conditions. We believe MariTide has the potential to expand what's possible for patients, availing an opportunity for monthly or less frequent dosing. MariTide's strong efficacy, infrequent dosing, and excellent tolerability at target dose have the potential to further enhance the patient experience and therefore treatment persistence, a major unmet need in the field. Beyond obesity and general medicine, the fourth quarter brought a landmark contribution to cardiovascular health from Repatha.

In November, full results from the phase III VESALIUS-CV trial were presented at the American Heart Association Scientific Sessions and simultaneously published in The New England Journal of Medicine. This study enrolled more than 12,000 patients without a prior heart attack or stroke, testing the impact of Repatha for LDL-C lowering when added to optimized lipid therapy, namely statins, with a median follow-up of approximately 4.5 years. In VESALIUS-CV, Repatha demonstrated a 25% relative risk reduction in the composite of coronary heart disease, death, heart attack, or ischemic stroke, and delivered a 36% reduction in heart attack, with no new safety signals observed. These data clearly demonstrate that intensive LDL-C lowering with Repatha can meaningfully reduce the risk of a first cardiovascular event, reinforcing its role across the full continuum of cardiovascular risk.

Turning to Olpasiran, our potentially best-in-class, small interfering RNA medicine targeting Lp(a), the fully enrolled OCEANA outcome study continues to progress. As previously discussed, this is an event-driven study, and the aggregate endpoint accrual rate remains lower than initial predictions. As this study matures, we will update on the date for primary analysis as appropriate. Our conviction in Olpasiran to reduce cardiovascular risk conferred by elevated Lp(a) remains strong, grounded in compelling genetic and epidemiologic evidence that establish elevated Lp(a) as an independent risk factor for heart disease. Moving to rare disease, the fourth quarter was highlighted by important regulatory momentum for Uplizna. In November, the European Commission approved Uplizna for the treatment of adults with active IgG4-related disease, and in December, the FDA approved Uplizna for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor or anti-MuSK antibody positive.

These approvals built on strong phase III data, demonstrating durable efficacy, a steroid-sparing benefit with every six-month dosing. This research further extends the impact of CD19-directed B-cell depletion across serious autoimmune diseases. More broadly, in B-cell depletion, where we have a number of proof-of-concept studies underway, we expect to initiate two pivotal studies this year. The first is for patients with autoimmune hepatitis, a serious disease characterized by persistent liver inflammation that can lead to progressive scarring, loss of liver function, and ultimately liver failure. The second studies chronic inflammatory demyelinating polyneuropathy, or CIDP, a disabling immune-mediated neuropathy that damages peripheral nerve myelin, resulting in worsening strength, worsening sensation, and for many patients, substantial impairment in daily activities. With Uplizna, we are targeting these diseases at their root cause by depleting pathologic B cells that drive disease through secreted autoantibodies.

Given the strong efficacy of Uplizna in other settings, we're excited about the potential to bring a meaningful new option to patients with these two devastating conditions. We are also advancing Dazodalibep, our CD40 ligand-targeting biotherapeutic, with both phase III studies in Sjögren's disease now fully enrolled and study completion expected in the second half of 2026. We're pleased today to announce positive phase II data with Daxdilimab, a first-in-class plasmacytoid dendritic cell-depleting monoclonal antibody targeting ILT-7, or the immunoglobulin-like transcript seven protein. This study in patients with primary discoid lupus erythematosus met both primary and key secondary endpoints with an attractive safety profile. Encouraged by these data, we are working to advance Daxdilimab to the next phase of development in this setting.

In inflammation, the Tezspire Phase III program continues to advance, with ongoing studies in chronic obstructive pulmonary disease and eosinophilic esophagitis, where we expect study completion in the second half of this year. We recently announced the decision to terminate the Rocatinlimab development and commercialization collaboration with Kyowa Kirin. With significant breadth and depth across all four therapeutic areas, we took a portfolio decision to focus resources on other late-stage programs. Rocatinlimab will return to our partners at Kyowa Kirin, who will assume full ownership of the program. Turning to oncology, in November, the FDA granted full approval to Imdelltra for the treatment of adult patients with extensive-stage small cell lung cancer, with disease progression on or after platinum-based chemotherapy. This approval represents a meaningful advancement for patients facing a disease that has seen very little innovation for decades.

To extend the impact of Imdelltra, we are presently advancing this medicine as combination therapy in frontline extensive-stage small cell, where we observed unprecedented survival in early phase clinical trials. Further, we are also advancing Imdelltra with an ongoing phase III study of limited-stage small cell lung cancer. It's a joy to see Imdelltra, like Blincyto, becoming a standard of care in the management of advanced cancer. Our first-in-class STEAP1-directed bispecific T-cell engager, Xaluritamig, continues to advance through phase III development in prostate cancer. Beyond prostate cancer, we have recently initiated a phase I-B study in relapsed or refractory Ewing sarcoma, a rare malignancy with high STEAP1 expression in patients in an urgent need for targeted therapy. Across Imdelltra, Blincyto, and Xaluritamig, we continue to see meaningful long-term impact from our bispecific T-cell engager platform.

We remain committed to bringing transformative and innovative therapies like these to patients with cancer. To close out oncology, given the previously announced results from FORTITUDE-101 and FORTITUDE-102, we have decided not to pursue regulatory approval for Bemarituzumab, our FGFR2B-targeting monoclonal antibody in first-line gastric cancer. Though overall efficacy did not meet our expectations, we observed an emerging signal of putative survival benefit in a subset of biomarker-defined patients. We expect to share these findings with the scientific community in the future. As with rocatinlimab, we took a portfolio decision to focus resources on our other late-stage programs. Across biosimilars, both ABP 206 and ABP 234 biosimilar candidates to Opdivo and Keytruda, respectively, have completed enrollment in each of their comparative clinical studies, supporting continued progress of the next wave of our biosimilar portfolio.

Before closing, as described in our press release, we are engaged in an ongoing dialogue with the FDA regarding Tavneos, our medicine for the treatment of a rare and severe disease, ANCA-associated vasculitis. We will update you on those discussions as necessary. Now, let me finish by saying that 2025 was a year of consistent execution, real scientific progress, and disciplined decision-making. We expect 2026 to bring another year of strong execution, disciplined data generation, and new scientific advances as we continue to progress our robust pipeline. I want to thank our colleagues across Amgen for their continued focus on patients and their commitment to advancing innovative medicines for serious diseases. With a broad and deep pipeline, we are well positioned to deliver sustained long-term growth. I'll now turn it over to Murdo for the commercial update.

Murdo Gordon (EVP of Global Commercial Operations)

Thanks very much, Jay. In 2025, we delivered 10% sales growth, with 13 products achieving double-digit or better performance. 14 products exceeded $1 billion in annual sales, and 18 products achieved record sales. These results underscore the strength and growth potential of our portfolio and demonstrate the disciplined execution of our teams serving patients globally. Starting with general medicine, Repatha sales grew 36% year-over-year in 2025, surpassing $3 billion. This performance was driven by growing urgency to treat patients in both secondary and primary prevention. Today, more than 100 million people around the world still need effective LDL cholesterol lowering, and Repatha remains the first and only PCSK9 inhibitor with outcomes data for patients in both high-risk primary and secondary prevention.

As Jay mentioned, the landmark VESALIUS-CV trial showed a reduction in the risk of first major cardiovascular events by 25% in high-risk patients. These data strengthen Repatha's position as the most evidence-backed therapy in the PCSK9 class and support this critical role in earlier and more intensive LDL cholesterol management. Given these results and our leadership in this category, we believe there's now a clear opportunity to update clinical guidelines and quality measures. We expect these changes will encourage cardiologists and primary care physicians to manage LDL cholesterol more proactively, alongside lifestyle modification, and reduce cardiovascular risk in both primary and secondary prevention. In the U.S., we continue to improve patient access to Repatha with broad formulary coverage and the launch of Amgen Now, our new direct-to-patient program. Amgen Now offers a simplified, lower-cost cash pay option for patients to access Repatha.

Following a successful launch, we've announced plans to expand this program to additional medicines, and we're excited to make our therapies available through TrueRx, helping improve affordability for Americans. Evenity sales increased 34% in 2025, reaching $2.1 billion in sales. Evenity remains the only treatment that simultaneously builds new bone and reduces bone resorption, a dual mechanism that is proven to rapidly reduce fracture risk in the post-menopausal women. In the U.S., Evenity sales grew 41%, driven by higher volumes from both established and new prescribers. Evenity leads the bone builder segment with over 60% market share and is now growing faster than the category overall. To date, approximately 300,000 U.S. patients have been treated with Evenity, with a 33% increase of new patients in just one year.

Increased investment has helped accelerate this growth, which we expect to continue. Despite strong progress, nearly 90% of the two million women at very high risk of fracture remain untreated, presenting a clear opportunity for Evenity to drive growth and impact. Prolia delivered $4.4 billion in sales in 2025, an increase of 1% year-over-year. In 2026, we expect accelerated sales erosion driven by increased competition as multiple biosimilars have launched globally. Our rare disease portfolio grew 14% year-over-year to nearly $5.2 billion and 19% in the quarter, with strong performance across the portfolio. Uplizna sales increased 73% year-over-year to $655 million, reflecting growing patient demand across all three approved indications.

In December, Uplizna received FDA approval for the treatment of generalized myasthenia gravis, marking an important milestone for patients with this chronic, debilitating disease. Early physician response has been strong across both bio-naive and switch patients. Prescribers have noted the benefits of Uplizna's upstream B-cell mechanism, targeting the root cause of the disease, and it also has demonstrated safety profile and the convenience of its twice-yearly dosing. Uptake of Uplizna for use in IgG4-related disease continues to grow. Since the launch in the U.S., nearly 500 specialists, including rheumatologists, gastroenterologists, among others, have prescribed Uplizna. In addition to the more recent launches, Uplizna continues to lead in NMOSD and remains the most prescribed FDA-approved therapy in the U.S. for this condition, supported by consistent new patient growth and strong adherence across treatment cycles.

Tepezza grew 3% to $1.9 billion in 2025, driven by higher net selling price. Over 25,000 patients have received treatment since launch in the U.S., with growing interest from both new and returning prescribers. We continue to see increased prescribing by endocrinologists and a broadening base of specialists. In Japan, approximately 1,200 patients have been treated since launch, reflecting growing awareness of the burden of thyroid eye disease among both patients and prescribers. We plan to launch Tepezza in additional markets in 2026, expanding access to this important therapy globally. Tavneos sales were $459 million in 2025, an increase of 62% year-over-year, driven by strong volume growth.

More than 7,000 patients with ANCA-associated vasculitis have now been treated with Tavneos, with over 4,000 healthcare professionals prescribing the therapy since its launch in 2021. ANCA-associated vasculitis is a serious, potentially life-threatening disease that can cause significant organ damage, if not well controlled, and has limited therapeutic options. We remain confident that Tavneos is an important and effective medicine based on clinical data, real-world evidence, and its favorable benefit-risk profile. In inflammation, Tezspire sales grew 52% year-over-year to nearly $1.5 billion for the full year. Tezspire is well-positioned to reach more patients in the United States due to its differentiated TSLP mechanism that targets multiple inflammatory pathways, driving severe uncontrolled asthma, including in those with coexisting chronic rhinosinusitis with nasal polyps. Tezspire substantially reduced the need for surgery in this population, reinforcing its value in eosinophilic disease.

Tezspire is now the leading therapy for new-to-brand patients amongst allergists in severe uncontrolled asthma, fueled by strong prescriber confidence and continued expansion across respiratory specialties. Otezla sales increased 7% year over year to nearly $2.3 billion for 2026. We expect sales erosion driven by unfavorable pricing in the U.S. and generic launches, particularly in the EU. Our innovative oncology portfolio, which includes Blincyto, Imdelltra, Lumakras, Vectibix, Kyprolis, Nplate, and Xgeva, grew 11% year over year, generating $8.7 billion in full-year sales. Imdelltra delivered $627 million in full-year sales, fueled by strong clinical conviction and rapid adoption across care settings. Over 1,600 U.S. sites now administer Imdelltra, with the majority of doses provided in the community setting.

Imdelltra was granted full FDA approval in the fourth quarter, supported by compelling data from the phase III DeLLphi-304 trial... NCCN guidelines also recognize Imdelltra as the highest recommended therapy, and it has become the standard of care in the second-line setting, reinforcing its leadership position in small cell lung cancer. Blincyto grew 28% year-over-year to over $1.5 billion in full year sales, driven by broad prescribing across both academic and community settings. Blincyto is widely recognized as the standard of care in combination with multi-agent chemotherapy for patients with Philadelphia chromosome-negative B-cell ALL. Our biosimilar portfolio delivered another strong year, with sales increasing 37% to $3 billion. Our expanding biosimilar portfolio provides meaningful top-line growth, durable cash flow, and broad patient access to high-quality, cost-saving biologic medicines.

Pavblu, a biosimilar to Eylea, continues to gain momentum, reaching $700 million in sales in 2025. Adoption continues to build among retina specialists who value the product's ready-to-use, prefilled syringe format and the reliability of Amgen's manufacturing and supply chain. We deliver strong results in 2025, with continued momentum across our priority growth brands, and we look forward to serving even more patients with Amgen products in 2026. Now, I'd like to hand it over to Peter.

Peter Griffith (CFO)

Thank you, Murdo. We're pleased with our execution and performance in the fourth quarter and for the full year 2025, and we remain on track with our long-term objectives. The financial results are shown on Slides 34 to 36 of the slide deck. Murdo's covered our strong revenue growth across the portfolio. For the full year, we delivered a Non-GAAP operating margin of 46%. We continued to invest in advancing our pipeline with non-GAAP R&D spending increased 22% year-over-year for the full year to a record $7.2 billion. This reflects increased spending on an unprecedented number of opportunities in our late-stage pipeline, including continued investments in MariTide, Olpasiran, Xaluritamig, and rare disease. In addition, we closed several business development transactions in the third and fourth quarters, resulting in roughly $300 million in incremental R&D spending.

Full-year non-GAAP other income and expense was $2.1 billion. We continued to strengthen our balance sheet with $6 billion of debt retired in 2025. Our non-GAAP tax rate increased 1.4 percentage points year-over-year to 15.9% for the full year, primarily due to changes in earnings mix. We generated $8.1 billion in free cash flow for the full year, reflecting operational momentum across the business and rigorous management of working capital, all while continuing to invest in innovation. We're leveraging AI across the value chain to accelerate therapeutic discovery and late-stage development, optimize manufacturing, and improve customer engagement, allowing us to drive productivity at speed and scale. We executed capital expenditures of $2.2 billion in 2025.

Our capital expenditures reflect significant investments across the United States, including Ohio, North Carolina, Puerto Rico, Rhode Island, and California, to support continued volume growth in our commercial brands and to prepare for pipeline product launches, including MariTide. In addition, we returned capital to shareholders through competitive dividend payments of $2.38 per share in the fourth quarter, representing a 6% increase compared to 2024. Let's turn to the 2026 outlook on Slide 37. We expect our 2026 total revenues in the range of $37.0 billion-$38.4 billion and non-GAAP earnings per share between $21.60 and $23. Our revenue range reflects continuing strong performance from our 6 key growth drivers: Repatha, Evenity, Tezspire, our rare disease, innovative oncology, and biosimilars portfolios, positioning 2026 as a springboard year for future growth.

We expect this growth in 2026 to more than offset anticipated declines from increased denosumab biosimilar competition, price declines for certain other products in 2026, and continued increases in 340B program utilization. As you model the first quarter of 2026, consistent with historical trends tied to the annual United States health insurance cycle, we expect a seasonal headwind to sales driven by benefit plan changes, insurance reverifications, and higher patient copay obligations. We also expect Otezla and Enbrel to follow their historical pattern of lower sales in the first quarter relative to subsequent quarters, and expect additional impact from denosumab biosimilar competition in Q1. Additionally, note that we saw roughly $250 million of inventory build in the fourth quarter of 2025 that could potentially impact first quarter sales.

For total company revenues, we expect lower mid-single-digit year-over-year growth in the first quarter. For the full year, we expect other revenue in the range of $1.6 billion-$1.8 billion, reflecting our commitment to investing in the best innovation, while also driving execution excellence, efficiency, and prioritization across the organization. We project the full-year non-GAAP operating margin as a percentage of product sales to be roughly 45% to 46%. This guidance does not include any potential business development transactions that may occur throughout the year. We expect non-GAAP R&D expense to grow low single digits, excluding the roughly $300 million of business development transactions in 2025. We continue to execute six global phase III clinical trials for MariTide, advance additional late-stage assets, and invest in the best innovation while maintaining disciplined resource allocation.

In line with lower product sales in the first quarter, we expect Q1 non-GAAP operating margin to be the lowest of the year and roughly the same as Q4 of 2025. We anticipate non-GAAP other income and expense to be about $2.3 billion to $2.4 billion in 2026. We expect a non-GAAP tax rate of 16% to 17.5%. We expect share repurchases not to exceed $3 billion in 2026. We expect capital expenditures of about $2.6 billion in 2026. This is consistent with our capital allocation priority to invest in our business and scale manufacturing capacity for volume growth, including preparing for MariTide launch.

We remain focused on delivering sustained long-term growth and creating value for patients and shareholders by doing what we said we would do, advancing innovation in areas of high unmet medical need and maintaining rigorous financial discipline. I'm grateful to work with all of our colleagues worldwide in serving patients. This concludes the financial update, and now I'll hand it back to Bob for Q&A.

Robert Bradway (CEO)

Okay, thank you, Peter, and as I hope you all appreciate now, I think we ended 25 with our track record intact for having delivered against the objectives that we set for you at the beginning of the year, and we're determined to do the same now in 2026. So we're entering the year with momentum, excited about what we see ahead. Let's open up the call to questions, Julianne. We'd be happy to entertain any of our callers now.

Operator (participant)

Thank you. If you would like to ask a question, please press star, followed by one on your telephone keypad. If for any reason you would like to remove that question, please press star followed by one. Again, to ask a question, press star one. Our first question comes from Michael Yee from UBS Financial. Please go ahead. Your line is open.

Michael Yee (Analyst)

Hey, guys. Good afternoon, and thanks for all the color, and looks like guidance is growth for the year, despite the biosimilars. Obviously, obesity is top of mind for everybody, and you've disclosed some information on MariTide recently. I was wondering and curious to ask your view of the portfolio overall in obesity, given that folks like today are disclosing combinations with monthly or monthly and then combinations, and how you see this playing out, given you're focused on MariTide, but not so sure about the rest of the portfolio there. Thank you.

Robert Bradway (CEO)

Okay. Thank you, Michael. We'll take a stab at answering your question. Connection wasn't great, but I think we got most of what you were trying to ask. Jay, you want to kick off?

James Bradner (EVP of Research and Development)

Yeah, I'd be happy to. Thanks, Michael. Amgen's really made for this moment, developing MariTide across so many different indications, a leading cardiovascular company, also a leading respiratory disease company, and there are so many opportunities there for MariTide. We've been in obesity, as you know, a long while, all the way back to the leptin days, and enjoyed stable discovery leadership team since that time. Internally, we have another clinical stage asset, called AMG 513. We have yet to disclose the mechanism of that medicine. It is progressing in phase I clinical investigation. Pre-clinically, we have a rather exciting set of nascent programs that are both incretin-based as well as non-incretin-based, both injectable as well as oral medicines, and the aperture is always open for innovation on the outside.

Robert Bradway (CEO)

I think you should expect us to be competing broadly in the field, Michael. Okay, let's move on. Next question.

Operator (participant)

Thank you, Michael. Our next question comes from Yaron Werber, from TD Cowen. Please go ahead. Your line is open.

Yaron Werber (Managing Director)

Great. Thanks so much. I have a question actually about dazodalibep for primary Sjögren's syndrome. It looks like both studies are now fully enrolled, and you're saying completion in the second half. You're the only company with both a systemic and a symptomatic study in phase III, based on the phase IIs. Should we expect the data this year, and do you want to give us any color on the reliability of the phase II into the phase III? Just given it's a tough condition. Thank you.

James Bradner (EVP of Research and Development)

Thanks, Yaron. And thanks for noticing about dazodalibep. This is a very exciting medicine in the portfolio. This is a CD40 ligand targeting biotherapeutic, and the CD40 pathway has long been postulated to be driving the inflammatory cascade in Sjögren's syndrome. The challenge is only that the biology is somewhat ambiguous, and so we take a really nice and incisive approach with dazodalibep in this disease. As you noted, the two phase IIIs that we have open in Sjögren's syndrome will be in moderate to severe symptomatic activity. That's our population one, as well as in patients with a very high symptom burden. That's population two. Sjögren's has been very challenging for drug development, but we find this hypothesis quite compelling. The second study has already completed enrollment of patients.

This is the moderate to high symptom burden group with low systemic disease activity, and we expect completion of the trials later this year, and we'll inform later about our plan to communicate this information. As for reading through the reliability of phase II into phase III, there have been historic challenges here, but the performance against this SDI score, which is the clinically utilized as well as regulatory paradigm for approval, you know, was one of the first medicines ever to improve an SDI score in that disease space. So, we're confident going into phase III and can't wait to look at the results.

Operator (participant)

Thank you, Yaron. Our next question comes from David Amsellem from Piper Sandler. Please go ahead. Your line is open.

David Amsellem (Managing Director)

Hey, thanks. So I had a couple of Uplizna-related questions. Can you talk about the extent to which the underlying IgG4-related disease population is larger than what literature has suggested historically and what that means for the underlying opportunity? And then secondly, I know it's early in GMG, but can just—can you talk about how the product's being used to date, and what kind of role do you think it's gonna have in the in an admittedly more crowded treatment armamentarium? Thanks.

Robert Bradway (CEO)

Yeah, let's. Why don't we tackle this in two parts. Jay, if you take the first part, and then maybe, Murdo, you can jump in on the second. Go ahead.

James Bradner (EVP of Research and Development)

You know, there is, in medicine, an experience where the availability of a targeted therapy, a really effective therapy, can actually increase the incidence of a disease through awareness of the disease. Why take a diagnosis unless you have reason to, to intervene effectively? And that may, in the fullness of time, be the case here. Limiting a precise description of the epidemiology, even over the last five to 10 years, is the lack of really coherent registry data, as well as appropriate coding that would allow, such an analysis from, electronic medical record data. And so I think it's a good question. I think it's a, a moving object, and we'll have better precision on that in a few years to come. Myrtle, what are your instincts?

Murdo Gordon (EVP of Global Commercial Operations)

I think that's a very clear description, Jay. I think the availability of the ICD-10 coding, as you alluded to, is really about a three-year presence in the market. Right now, we estimate the diagnosed population to be in the neighborhood of 35,000, and that could grow. As you outlined, there are mentions in the literature of higher numbers. However, we're obviously focused on those that are already diagnosed, already in care, and we're trying to build that awareness that you spoke of, Jay. So far, so good. Uplizna is doing extremely well in its uptake in IgG4-related diseases. We see a nice breadth of prescribing across a number of different specialties that see these patients because of the end organ involvement in the inflammatory condition.

We'll continue to make sure that we do our part to improve that awareness, improve that diagnosis. These patients undergo a very complicated patient journey, in that this disease can masquerade as many other things. But, so far, so good, and, and we're happy to be able to help these patients finally, get a treatment, the only one FDA approved, that can help with their symptoms and obviously the long-term health outcomes, particularly for their target, organs. Just on Uplizna and GMG, we're, we're very pleased with the initial uptake. As you said, David, it's very early in the launch, but, what we're pleased about, and I, I mentioned this in, in my opening remarks, is that roughly half of the patients who are being treated are bio-naive patients, and the other half coming from switches from other therapies.

As we've said before, this is a large but still quite dissatisfied category where the current treatments have limitations, whether that be dosing inconvenience, whether that be duration of efficacy and perhaps some waning efficacy in this category. And so far, what we've seen is a very strong interest in Uplizna for its mechanism, as well as for the convenience that it represents for patients. So, so far, so good. Excited about Uplizna overall in the broader rare disease portfolio.

Robert Bradway (CEO)

Okay, thanks. Let's go to the next question.

Operator (participant)

Thank you, David. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Your line is open.

Salveen Richter (Analyst)

Good afternoon. Thanks for taking my question. Just a follow-up here on Uplizna. Walk us through what's given you confidence here in moving forward with a phase III study in CIDP and the opportunity in that indication. And if you could also just separately touch on Repatha and how you're thinking about potential impact from the launch of Merck's oral PCSK9, and how you're adapting your commercial strategy there. Thank you.

Robert Bradway (CEO)

With two ends of a spectrum there, from the very rare to the, to the very common. So let's do, Jay, you do the first question, and then, Murdo, you can take second.

James Bradner (EVP of Research and Development)

Okay. Thanks, Selene. We are, as Myrtle shared, very bullish about Uplizna, specifically this unique mechanism of action that targets and depletes the CD19 pathologic B-cell. These, as you surely know, CD19, the B-cell compartment, is evident on mature B-cells, like CD20, targeted by, rituximab and other medicines of that type, but also the pre-B cell, the more naive B-cell, the cell that expands and elaborates many of these autoantibodies. And so now, seeing efficacy of Uplizna in so many immunoglobulin-related disorders, like IgG4-related disease, like myasthenia gravis, the chance to bring it to additional, autoantibody-mediated immune conditions, is just a great chance to help patients with these severe diseases. In some cases, there are signals from CD20s that we intend to follow up with a broader, more active, and hopefully much more convenient, Uplizna.

Autoimmune hepatitis, which I mentioned earlier, is associated with autoantibodies. You see ANA, you see anti-smooth muscle, you see anti-actin, you see anti-LC1. And the same is true, though to a lower proportion, with CIDP as well, where maybe 5% to 10% of patients will have autoantibodies to what are called perinodal proteins, NF155, CNTN1. I could go on for a long time. And so this biology being driven by the compartment that Uplizna targets makes for a really great chance to extend the benefits of targeting B cells in both of these conditions. Murdo?

Murdo Gordon (EVP of Global Commercial Operations)

Yeah, just the size of the opportunity here is interesting. Roughly, the prevalent pool in the U.S. is estimated to be about 35,000 patients, maybe 7,000 to 10,000 incident new diagnosed cases per year in the U.S. So, hopefully, we can develop this drug and offer some benefit for these patients, which is yet another steroid-intensive condition, and we believe that we can do better than that. So let's hope for that best outcome in those clinical trials. On Repatha, I alluded to what our strategy is in my opening remarks.

We are excited by the landmark data that were revealed at the American Heart Association last year in November, where we can now clearly promote Repatha for the prevention of first heart attack or first stroke in a high-risk patient population or and/or a high-risk primary prevention population. And so, that is our focus right now, and we are the only PCSK9 that has both secondary and primary prevention data in our label. The VESALIUS data are being met very positively by both cardiologists and primary care physicians, in particular for the primary care physician, for the diabetes patients that were enrolled in the trial, who did very well. So we are focused on making sure there's high awareness of these data.

Repatha enjoys great access, broadly preferred on national template formularies by PBMs and health plans around the country and around the world. And of course, we, we know that there's an immense amount of trust now in the profile by prescribers. And for the millions of patients that have received treatment and are taking Repatha, there's strong acceptance that a every two-week injection to lower cholesterol to the 45 mg per dl target dose that was achieved in the Repatha arm in FOURIER, so that patients can reduce their cardiovascular risk. So we've got a lot to talk about.

We've maintained all along that there is a lot of room in this market for other therapies to come in, but they will not have the data package and profile that Repatha has established, and we'll continue to remind prescribers and others about that. Thank you.

James Bradner (EVP of Research and Development)

Okay, let's go to the next question.

Operator (participant)

Thank you, Salveen. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Mohit Bansal (Analyst)

Great. Thank you very much for taking my question, and congrats on all the good progress here. Maybe, like, just, again, the question on PCSK9, and Repatha at this point. So, Murdo, can you please remind us what percentage of your prescriptions are coming from primary care at this point? And with the VESALIUS data, like, how do you see the primary care segment of the market evolving over time? Thank you.

Murdo Gordon (EVP of Global Commercial Operations)

Yeah. Thanks, Mohit. I put a number out before the VESALIUS data promotion started, where roughly 40% of our prescriptions were coming from patients who were considered primary prevention, patients who have not yet had an event, where physicians were looking to lower those patients' LDL cholesterol. I would imagine that that will increase and grow over time. What we're seeing is equal interest, quite frankly, from cardiologists who are excited by the VESALIUS data and the consistency of both the primary endpoint, the secondary endpoint, the MI subgroup. Quite frankly, the overall incidence of death in the trial was also something that attracted attention from specialists. So, the cardiology group has seen this as an affirmation of what they were already doing and being aggressive in treating LDL cholesterol.

Primary care physicians, as I mentioned, are much more intent and aligned to adding Repatha to the optimized statin therapy that most patients are on. As for how much, we don't give product specific guidance, but hopefully, you can tell I am extremely excited about the momentum that we have on Repatha right now. I'm really pleased with the execution of our teams around the world. We've made incremental investments in advance of the opportunity of promoting the VESALIUS data, and I expect that momentum to continue.

James Bradner (EVP of Research and Development)

Okay. Thank you. Let's go to the next question.

Operator (participant)

Thank you, Mohit. Our next question comes from Louise Chen from Scotiabank. Please go ahead. Your line is open.

Louise Chen (Analyst)

Hi. Thanks for taking my question. I wanted to ask you about Tepezza and your thoughts on another potential competitor coming to market, and then also where you stand with AMG 732 for TED. Thank you.

Robert Bradway (CEO)

Okay, great. Maybe, again, we could do this in two chunks. Jay, you want to talk about the-

James Bradner (EVP of Research and Development)

Sure.

Robert Bradway (CEO)

Clinical piece, and then Murdo, talk about the clinical piece?

James Bradner (EVP of Research and Development)

Thanks, Louise. Tepezza is proving to be just a very important medicine for the management of thyroid eye disease. We have established a very strong evidence base in both the high clinical activity score and lower clinical activity score patient populations, and are quite proud of this data generation and also the apparent impact that it's having on patients being treated today. We have a ongoing subcutaneous phase III clinical study, a moderate to severe active TED, fully enrolled, as we have shared, and we expect to complete this study in the second half of this year. So we have a really terrific medicine that's increasingly a standard of care, that's helping a lot of patients, and a strong data set that it sits on top of.

Before handing off to Murdo, I'll just quickly comment on AMG 732. Thank you for noticing. This is an IGF-1R targeting monoclonal antibody, also achieves subcutaneous administration. Phase II study's enrolling, initially studied in moderate to severe and active TED, and we'll have more to say on that in the future. Murdo?

Murdo Gordon (EVP of Global Commercial Operations)

Yeah, thanks, Jay. As Jay mentioned, we're expanding our treatment for patients with thyroid eye disease into the lower clinical activity score patient population, who tend to be managed by different specialists than the higher clinical activity score patients. We have historically been able to drive very strong penetration with oculoplastic surgeons and general ophthalmologists. We're expanding our prescribing base to include endocrinologists. We made investments at the beginning of last year, and those investments are starting to return now by an increased base of endocrinologists prescribing. So that's in the U.S., and we expect that we'll continue to broaden our treatment of the low clinical activity score patients while maintaining our share of the higher clinical activity score patients. But also our international launches. Our launch in Japan has gone extremely well.

We're seeing nice uptake there. We're seeing a very well-received product for higher clinical activity score patients, and we're in the process of launching in multiple markets around the world as we speak. So, overall, Tepezza will be a good growth driver for us this year.

Robert Bradway (CEO)

Thank you. Let's go to the next question.

Operator (participant)

Thank you, Louise. Our next question comes from Terence Flynn from Morgan Stanley. Please go ahead. Your line is open.

Terence Flynn (Managing Director)

Hi, thanks for taking the question. I had one on the MariTide phase III program. Appreciate all the details today, but just was wondering if you have any update in terms of how to think about the design of the type II diabetes CVOT trial, particularly the control arm, as I know that's something that you guys were debating here post the, you know, seeing some of the data from some of the competitors, but just wondering how you're thinking about control arm in that setting. Thank you.

Robert Bradway (CEO)

Sure. Jay, you want to-

James Bradner (EVP of Research and Development)

Sure, I'm happy to share, Terence. We're just thrilled by the opportunity to develop MariTide for patients with type II diabetes, and this is really where we see a potential paradigm shift in the management of that disease. In my medical training, we practiced with insulin and insufficient orals and titrating dosing, and here we have a medicine that can be dosed monthly. We've seen efficacy in chronic weight management bi-monthly. We've recently described maintenance approach using quarterly dosing. This is just a new paradigm in management of diabetes. We've shared the major insights at J.P. Morgan from the phase II type II diabetes study, which is ongoing. There are additional parts to this trial. It's importantly given us an experience with low BMI patients and also seeing A1C across the dose range.

The robust findings of this trial position us very well to start to pursue phase III clinical investigation. The specific design of these studies, control arms, and the patients recruited will be a subject for a future engagement.

Robert Bradway (CEO)

Okay, thank you. Let's go to the next question.

Operator (participant)

Thank you, Terence. Our next question comes from Chris Schott from J.P. Morgan. Please go ahead. Your line is open.

Chris Schott (Analyst)

Great. Thanks so much. Just another MariTide question, and just on the topic of less frequent than monthly dosing. It certainly seems like there could be a trade-off here, where even more infrequent dosing, you know, would obviously be a huge benefit, even if it was associated with a bit less weight loss. I guess, so as you're thinking about just pushing the program beyond monthly, what profile do you think you'd need to see for that to have a role in the market? Are there minimum efficacy bars you're looking at? And just in general, what is your confidence about the ability to push this beyond monthly? Thanks so much.

Robert Bradway (CEO)

Okay, that's an interesting question. Murdo, do you want to take a shot at what we think we see in the marketplace, and why we believe MariTide has the potential to address what is emerging as a very large, unmet need in the field?

Murdo Gordon (EVP of Global Commercial Operations)

Yeah. I'll make a few comments here, Bob. Thanks for the opportunity. I think it's pretty clear, as we look at the market as it exists today, that there's dissatisfaction with the weekly GLP-1s. And I think you can actually see that in a fairly dramatic way with the advent of oral sema and how rapidly it's been taken up in the market. That tells you that clearly patients and prescribers are looking for other opportunities. Now, what I like is the opportunity that we have to deliver what has been mentioned a couple of times in this call as a paradigm-changing therapy, and that's, you know, the ability to come into a weekly market, bring a monthly therapy that can achieve similar weight loss in a very well-tolerated regimen.

And then, for those patients who achieve their weight goal, for them to convert to every eight-week or every 12-week dosing regimen to maintain that weight and/or the metabolic benefits of their therapy, and I think that's a pretty compelling offering. I think that, we're targeting that kind of profile, and we'll have multiple ways of generating data to that effect.

Robert Bradway (CEO)

Chris, maybe we'll have Jay just address a piece as well. Go ahead.

James Bradner (EVP of Research and Development)

Yeah, Chris, thanks for the question. If you don't mind, I'm gonna reject part of the premise of your question. This idea of less frequent dosing being an absolute trade-off for efficacy, we're not certain that we will see that. Having observed the large majority of patients maintaining weight on low dose and on quarterly dosing, in the field of obesity, they call this the defended fat mass, and the capacity to avoid weight regain is a sign that the reset of body weight has been achieved. We have seen with all medicines to date, dose-ranging effects on weight loss, and here we might expect to see schedule-ranging effects on weight loss that would be individualized for patients. And so I wouldn't necessarily assume that we'll see a big trade-off with less frequent dosing of MariTide.

Robert Bradway (CEO)

Okay, thank you. Let's go to the next question.

Operator (participant)

Thank you, Chris. Our next question comes from Umer Raffat from Evercore ISI. Please go ahead. Your line is open.

Umer Raffat (Managing Director)

Hi, guys. Thanks for taking my question. I'm really, really lost today. I'm trying to figure out what happened all of a sudden. Why did FDA decide to ask you to pull the ChemoCentryx drug? Was there some litigation or some correspondence? Like, what prompted it in the first place? And then, if I dig in a little more specifically, they're saying that nine patients need to be readjudicated. Is that referring to the primary endpoint on week 26 remission or the week 52 sustained remission? I ask because the week 26 endpoint was non-inferior anyway, so even if you readjudicate those, it's still non-inferior. So I'm just really lost today.

Robert Bradway (CEO)

Okay. Well, Jay, as you addressed the question. You may wanna just start at the high altitude, remind people what Tavneos is, and say a few words about the disease that it addresses. It's obviously a very small product in our portfolio relative to the other things we have going on, but it may be a medicine that's less familiar to most of our callers.

James Bradner (EVP of Research and Development)

Yes, sir. Thanks, Umer, and just by way of background then, ANCA-associated vasculitis is a group of very serious, rare, and destructive inflammatory illnesses that targets blood vessels and can therefore damage vital organs like kidneys, lungs, skin, nerves, even heart. The prior treatment paradigm before Tavneos was quite toxic. Cyclophosphamide chemotherapy with azathioprine and rituximab, accompanied by long-term steroid use. And chronic use of steroids proved very common, but also very challenging. Hyperglycemia, dystrophy, bone health, mood disorders, immune suppression. And then enter Tavneos or avacopan. This is an oral complement C5a receptor blocker, and so it blocks complement-mediated destruction.

We acquired Tavneos from ChemoCentryx in 2022 after it had been on the market for a year, based on approval for the ADVOCATE phase III study that you referenced, as published in the New England Journal. This established the efficacy of Tavneos over prednisone steroid tapering for sustained remission out to 52 weeks when it was added to induction therapy with, at that time, standard of care rituximab and cyclophosphamide. As we shared, the FDA requested a voluntary withdrawal on January sixteenth. We were surprised by this. There were concerns raised about a process followed by ChemoCentryx to readjudicate primary endpoint results for nine of the 331 patients. We're in discussions with FDA, and we'll answer questions as we talk with them.

Robert Bradway (CEO)

Okay, let's go on to the next question.

Operator (participant)

Thank you, Umer. Our next question comes from Alex Hammond from Wolfe Research. Please go ahead. Your line is open.

Alex Hammond (Analyst)

Hey, guys. Thanks for taking the question. So you had another strong quarter with Pavblu. I guess, how do you kind of expect to maintain this leadership position when other manufacturers launch their biosimilars in the second half of the year? I guess, essentially, can you kind of help level-set growth expectations for this year?

Robert Bradway (CEO)

Well, obviously, we're not giving guidance on an individual product, Alex, but Murdo, go ahead and talk a little bit about the strong performance that we've observed so far for our biosimilar to Pavblu.

Murdo Gordon (EVP of Global Commercial Operations)

Well, yes, I think what we've been able to do thus far is establish good inroads with the largest national retina specialist networks. And the-- I think what I would say is they tend to want to pick a product that they know allows them to manage their patients effectively. We think we've got a great device that helps them do that. We obviously are competing effectively against the innovator, and given that, we have a lot of biosimilar experience, we'll compete effectively when others enter the market, whenever that may be.

Robert Bradway (CEO)

Okay, we'll take, well, one last question as we're right up against the bottom of the 30-minute mark here of the hour. So, why don't we take one last question, and then, as always, Casey and his team will be around to answer questions if we didn't get to you on this call. Julianne, last question.

Operator (participant)

Thank you, Alex. Our last question will come from Courtney Breen from Bernstein. Please go ahead. Your line is open.

Robert Bradway (CEO)

Okay, Courtney, bring us home.

Courtney Breen (Senior Research Analyst)

Thanks so much.

Fantastic. Thanks so much for squeezing this in. I am gonna bounce you back to MariTide, and just as we think about maintenance and that kind of less frequent dosing opportunity, can you describe how you might think about the role of this product in the market? Is it only post MariTide weight loss, or how should we be thinking about kind of that switching opportunity and the type of data that you might demonstrate for that positioning over time? Thanks so much.

Robert Bradway (CEO)

Yeah, I can imagine there's probably a lot of interest in that. Murdo, do you wanna share any thoughts at this point?

Murdo Gordon (EVP of Global Commercial Operations)

Well, thanks, Courtney. Obviously, we think we've got, as has been said now many times, and I'll repeat it again, a product that changes the paradigm of weight loss, diabetes, ASCVD, heart failure management. And, we see it as both, an effective product to start patients on, to get to weight goal, and also, for patients who, to receive the medical benefit of their treatment, need to be on these therapies for multiple years. This opportunity for MariTide's profile to deliver a convenient, well-tolerated, efficacious regimen that could be monthly, could be every eight weeks, and could be quarterly. We think that's really exciting. And then, of course, as you hinted at, there may be patients out there on other therapies that want to switch to something as convenient and as well-tolerated as MariTide.

So, the answer is all of the above.

Robert Bradway (CEO)

Okay. So, again, thank you all for your interest. We appreciate you joining our call. I'll just reiterate, if we didn't get to you, please reach out directly to Casey and his team. In the meanwhile, I hope we've left you confident about the momentum that we're carrying into 2026. And again, I would just reiterate that we're excited about the year that we have in prospect here, a year, which, as Peter has described, we view as a springboard to the future growth here at Amgen. So excited about the hand that we have and look forward to sharing it with you during the course of the year. Thank you.

Operator (participant)

This concludes our Amgen Q4 2025 Earnings Conference Call. You may now disconnect.