Amgen bets its decade on cardiometabolic moonshot as legacy blockbusters erode

A portfolio built for the patent cliff era

Amgen entered 2026 sounding almost defiant. On paper, the challenge is familiar: ageing franchises such as Prolia, Otezla and Enbrel are heading into sharper erosion as biosimilars, price pressure and 340B expansion bear down. Yet across the prepared remarks, management’s narrative was less about defence and more about breadth.

For 2025, Amgen delivered 10% sales growth, with 14 products now above the $1 billion “blockbuster” threshold and 18 posting record revenues. Non-GAAP operating margin held at a robust 46%, despite a 22% jump in R&D spend to $7.2 billion. Free cash flow reached $8.1 billion, allowing the company to retire $6 billion of debt, fund $2.2 billion of capital expenditure across multiple US manufacturing sites, and lift the quarterly dividend by 6% versus 2024.

Chief executive Robert Bradway framed 2025 as proof that Amgen’s diversification strategy is working: 13 products achieved double‑digit sales growth, underpinned by six “momentum” franchises – Repatha, Evenity, TestSpire, rare disease, innovative oncology and biosimilars. On that foundation, 2026 guidance calls for total revenue of $37–38.4 billion and non‑GAAP EPS of $21.60–23.00, with management characterising the year as a “springboard” to longer‑term growth even as denosumab biosimilars and pricing headwinds bite.

The financial picture, delivered by CFO Peter Griffith, contained a familiar seasonal warning: first-quarter revenues are expected to grow only low‑ to mid‑single digits year on year, pressured by the US insurance reset, denosumab biosimilars, lower Otezla and Enbrel sales and a $250 million inventory build from 2025 unwinding. Full‑year operating margin is guided at 45–46%, with share repurchases capped at $3 billion and capital expenditure rising to around $2.6 billion, in part to build out capacity for obesity candidate Meritide.

Cardiometabolic ambitions: Meritide, Repatha and opasiran

Beneath the diversified surface, Amgen is gradually reorganising itself around a cardiometabolic thesis. Bradway was explicit: taken together, Repatha, opasiran and Meritide “would represent a very compelling set of cardiometabolic medicines” capable of sustaining leadership in chronic disease “well into the next decade”.

Repatha is already the pillar of that vision. Sales rose 36% in 2025 to surpass $3 billion, driven increasingly by primary prevention. More than 100 million people globally still need effective LDL‑C lowering, management noted, and Repatha is now the first – and only – PCSK9 inhibitor with outcomes data in both high‑risk primary and secondary prevention.

The Vesalius‑CV trial, presented at the American Heart Association and published in the New England Journal of Medicine, has given Amgen a fresh lever. In over 12,000 patients without prior heart attack or stroke, Repatha on top of optimal lipid therapy (mainly statins) delivered a 25% relative risk reduction in the composite of coronary heart disease death, MI or ischaemic stroke, and a 36% reduction in MI, with no new safety signals. Those data, executives argued, should catalyse earlier, more intensive LDL management, guideline revisions and higher quality‑measure utilisation.

Commercially, Amgen is pairing evidence with new channels. In the US it has launched “Amgen Now”, a direct‑to‑patient cash‑pay programme designed to mitigate insurance friction and copay hurdles, and plans to expand the model to other brands. Management also flagged forthcoming availability through “Trump Rx” as it positions Repatha for broader, potentially more politically charged affordability debates.

Meritide, however, is the more speculative but transformative bet. The company’s GLP‑1–based obesity and diabetes candidate sat at the heart of both R&D chief James Bradner’s and commercial chief Murdo Gordon’s remarks. Six global Phase III studies – the Maritime programme – are now underway: two chronic weight management trials are fully enrolled, while ASCVD and heart failure outcomes studies are progressing. Two additional Phase III trials in sleep apnoea (with and without positive airway pressure) have begun enrolling, bringing the Phase III footprint to six indications.

Amgen has also completed part two of the VERITIDE Phase II chronic weight management study and the first 24 weeks of a Phase II type 2 diabetes trial enrolling both obese and non‑obese participants. Management said the results “further increased our confidence” that Meritide can be “paradigm‑changing”, emphasising three themes: strong efficacy, “excellent” tolerability at target dose, and the ability to dose monthly, every other month or even quarterly.

That dosing flexibility is where Amgen believes it can differentiate in a brutally crowded GLP‑1 market. Gordon painted a picture of rising dissatisfaction with weekly injectables, pointing to the rapid uptake of oral semaglutide as evidence that prescribers and patients are actively seeking alternatives. In Amgen’s ideal scenario, Meritide would secure weight loss comparable to weekly rivals with monthly dosing, then shift many patients to eight‑ or twelve‑weekly regimens for maintenance, extending persistence and making multi‑year therapy more palatable. Bradner, pushing back against the assumption that lower dosing frequency must mean compromised efficacy, noted that internal phase II data show most patients maintaining weight on low doses and quarterly schedules, suggesting that “schedule‑ranging” rather than dose‑ranging effects may become the key lever.

Beyond Meritide, Bradner reminded investors that Amgen has deeper roots in obesity biology than its public profile suggests, tracing back to the leptin era. AMG 513, an undisclosed obesity asset, is in phase I, and a suite of preclinical incretin and non‑incretin programmes – both injectable and oral – sit behind. The “aperture is always open” for external innovation, he added, implying Amgen is not ruling out bolt‑on deals.

Rounding out the cardiometabolic axis is opasiran, the company’s small interfering RNA targeting Lp(a). The fully enrolled, event‑driven OCEAN(a) outcomes study is accruing endpoints more slowly than initially modelled, a reminder that timelines could slip. Still, Bradner reiterated “strong conviction” in the programme, citing the robust genetic and epidemiologic case for Lp(a) as an independent cardiovascular risk factor. A positive OCEAN(a) read‑out would slot naturally alongside Repatha and Meritide, deepening Amgen’s claim to the cardiometabolic high ground.

Rare disease as a quiet growth engine

If cardiometabolic disease is Amgen’s headline, rare disease is becoming its quiet workhorse. The portfolio generated nearly $5.2 billion in 2025, up 14% for the year and 19% in the fourth quarter, with much of it still early in its lifecycle.

Aplisna – the CD19‑directed B‑cell depletor acquired via Horizon – is emerging as the centrepiece. Sales surged 73% to $655 million, supported by approvals in IgG4‑related disease in the EU and generalised myasthenia gravis (gMG) in the US. The twice‑yearly dosing schedule and “steroid‑sparing” efficacy profile have resonated with physicians facing chronic autoimmune diseases, and Amgen reports strong uptake in both biologic‑naïve and switch gMG patients.

In IgG4‑related disease, the company estimates around 35,000 diagnosed patients in the US, but both Bradner and Gordon hinted that true prevalence could be materially higher as awareness, coding and registries catch up now that a targeted therapy exists. Aplisna also continues to lead in neuromyelitis optica spectrum disorder (NMOSD) in the US, with consistent new patient growth and high adherence across treatment cycles. Amgen sees a clear path to expanding the drug’s footprint across the autoantibody‑driven disease landscape.

That ambition showed through in Bradner’s preview of two new pivotal programmes launching this year: autoimmune hepatitis, where B‑cell–driven autoantibodies propel insidious liver damage towards failure, and chronic inflammatory demyelinating polyneuropathy (CIDP), a disabling neuropathy with a subset of patients carrying specific paranodal autoantibodies. Both represent steroid‑heavy treatment paradigms in which a durable, upstream B‑cell depletor could change practice.

Further back in the autoimmune portfolio, Amgen is advancing desodilimab, a CD40 ligand‑targeting biologic for primary Sjögren’s syndrome. Two Phase III trials – one focused on systemic disease activity, the other on high symptom burden – are fully enrolled, with completion expected in 2026. Bradner described the biology as “ambiguous” but compelling, noting that phase II data showed one of the first improvements on the ESSDAI/SI score to be seen in this notoriously intractable condition.

The company also unveiled positive phase II data for daxdilimab, a first‑in‑class monoclonal antibody that depletes plasmacytoid dendritic cells via ILT7, in primary discoid lupus erythematosus. The trial met both primary and key secondary endpoints with an “attractive” safety profile, clearing the way for later‑stage development.

Other rare disease staples are still grinding higher. Tepezza, for thyroid eye disease, grew 3% to $1.9 billion, with over 25,000 US patients now treated and ~1,200 in Japan since launch. Amgen is extending its reach beyond oculoplastic surgeons and ophthalmologists into endocrinology and is enrolling a Phase III subcutaneous trial in moderate‑to‑severe active disease, due to complete in the second half of 2026. Early international markets are responding well, and AMG 732, an IGF‑1R‑targeting subcutaneous antibody, is in phase II as a potential follow‑on.

Tabneos (avacopan) was the blemish on the rare disease story. Sales rose 62% to $459 million on the back of growing use in ANCA‑associated vasculitis, with over 7,000 treated patients and 4,000 prescribers since its 2021 launch. But in January, the FDA unexpectedly requested a voluntary withdrawal, citing concerns about how ChemoCentryx, which Amgen acquired in 2022, handled readjudication for nine patients in the original ADVOCATE Phase III dataset. Bradner admitted Amgen was “surprised” and is now in active dialogue with the regulator; for investors, the episode is a reminder that legacy trial conduct can cast a long regulatory shadow.

Oncology: BiTEs ascend, gastric setback acknowledged

Oncology remains a core second pillar, with Amgen’s “innovative oncology” basket – including Blincyto, Imdeltra, Lumakras, Vectibix, Kyprolis, XGEVA and others – delivering $8.7 billion in 2025, up 11% year on year. The engine here is increasingly the company’s BiTE (bispecific T‑cell engager) platform.

Imdeltra (tarlatamab), targeting DLL3, has rapidly become the new standard of care in second‑line extensive‑stage small cell lung cancer (ES‑SCLC). Full FDA approval in November, based on the DELPHY‑304 Phase III trial, marked a rare bright spot of innovation in a disease that had seen “very little progress for decades”, as Bradner put it. The drug generated $627 million in 2025 – a sizeable figure for a first full year – with more than 1,600 US sites administering it, predominantly in community settings. It now holds the highest‑tier NCCN recommendation for its indication, anchoring Amgen’s claim that it is reshaping SCLC treatment standards.

Amgen is not stopping at second line. Imdeltra is being studied in frontline extensive‑stage SCLC in combination regimens, where early‑phase data showed “unprecedented” survival, and in a Phase III trial in limited‑stage disease. The clear intent is to march the BiTE technology earlier in the treatment sequence and across stages.

Blincyto remains another cornerstone, with sales up 28% to over $1.5 billion and broad uptake across academic and community haematology centres. The agent is now widely accepted as standard of care in combination with multi‑agent chemotherapy for Philadelphia chromosome‑negative B‑cell ALL, testament to the long‑term durability of Amgen’s original BiTE.

Zalaritamab, a first‑in‑class STEAP1‑targeting BiTE, is in Phase III development for prostate cancer and has just entered Phase 1b in relapsed/refractory Ewing sarcoma, a rare tumour with high STEAP1 expression and few targeted options. The company is increasingly portraying its BiTE franchise – across Blincyto, Imdeltra, zalaritamab and next‑generation constructs – as a platform, not a set of isolated assets.

Not all oncology efforts are succeeding. Amgen confirmed it will not seek regulatory approval for bimurtuzumab, its FGFR2b‑targeting monoclonal antibody in first‑line gastric cancer, despite “an emerging signal of putative survival benefit” in a biomarker‑defined subset from the FORTITUDE‑101 and ‑102 trials. Those data will be shared with the scientific community, but the company is redeploying resources towards other late‑stage assets. Similarly, Amgen has terminated its rocatinlimab partnership with Kyowa Kirin, handing that asset back as it prunes its inflammation portfolio to concentrate capital and attention on Meritide, TestSpire and other high‑priority programmes.

Inflammation and respiratory: TestSpire’s ascent amid portfolio pruning

In inflammation, TestSpire continued its steep climb. The anti‑TSLP biologic posted 52% year‑on‑year growth to nearly $1.5 billion in 2025, consolidating its position as the leading therapy for new‑to‑brand severe uncontrolled asthma patients among allergists. The drug’s appeal lies in its upstream mechanism – targeting TSLP, a key epithelial cytokine, to modulate multiple inflammatory pathways – and in data suggesting it can substantially reduce the need for surgery in patients with coexisting chronic rhinosinusitis with nasal polyps, bolstering its value proposition in eosinophilic disease.

Phase III programmes in chronic obstructive pulmonary disease and eosinophilic oesophagitis are on track to complete in the second half of 2026, potentially unlocking further respiratory indications. Against that backdrop, the decision to exit rocatinlimab underscores Amgen’s willingness to make unflinching portfolio calls in order to ring‑fence capital for assets with clearer commercial and mechanistic tailwinds.

Not all inflammatory mainstays are on such a trajectory. Prolia delivered modest 1% growth to $4.4 billion in 2025, but management warned of “accelerated sales erosion” in 2026 as multiple denosumab biosimilars launch globally. Otezla rose 7% in 2025 to nearly $2.3 billion, yet is expected to face heightened pricing pressure in the US and generic erosion, particularly in Europe, this year. Enbrel, while not dissected in detail, was flagged along with Otezla as following its traditional pattern of first‑quarter weakness and longer‑term headwinds.

On the osteoporosis side, Evenity offered a counterweight. Sales jumped 34% to $2.1 billion in 2025, with US revenues up 41% as both existing and new prescribers increased use. Evenity now leads the “bone builder” segment with more than 60% market share and is growing faster than the category. Amgen estimates that roughly 300,000 US patients have been treated, but stresses that nearly 90% of the 2 million women at very high fracture risk remain untreated – a substantial runway if diagnostic and referral gaps can be narrowed.

Biosimilars: scale, but still a sideshow to innovation

Amgen’s biosimilars business is now large enough to matter, but not yet dominant in the overall mix. Since launching its first biosimilar in 2018, the company has amassed over $13 billion in sales, with 2025 alone contributing $3 billion – a 37% year‑on‑year increase. Management reiterated the dual narrative: biosimilars provide “durable cash flow” and broaden patient access, while also funding the higher‑risk innovative pipeline.

Pavblu, Amgen’s biosimilar to Eylea, delivered around $700 million in 2025, emerging as a standout in the emerging ophthalmology wave. Retina specialists, the company says, particularly value its prefilled syringe format and Amgen’s manufacturing reliability. With multiple competitors expected to enter in the second half of 2026, investors pressed for clues on how growth might hold up; Gordon declined to provide product‑specific guidance but emphasised early wins with large retina networks and Amgen’s institutional experience in competing head‑to‑head with originators and biosimilar peers.

Next‑generation oncology biosimilars are already in the pipeline. ABP 206 and ABP 234, candidates to Bristol Myers Squibb’s Opdivo and Merck’s Keytruda respectively, have completed enrollment in comparative clinical trials, setting the stage for Amgen to ride the immuno‑oncology biosimilar wave later in the decade.

Management tone: confident, disciplined – and willing to cut

Beyond the data, the tone of Amgen’s prepared remarks was notable. Bradway repeatedly invoked the idea of a “springboard” year and a multi‑year arc of execution: 2025 ended with “our track record intact” against objectives set a year earlier, and 2026 is intended to do the same. The through‑line is discipline: in R&D, where the company has been willing to shutter bimurtuzumab and rocatinlimab; in capital allocation, where it has chosen to retire debt, invest in capacity and keep buybacks capped even as free cash flow expands; and in commercial strategy, where targeted direct‑to‑patient programmes such as Amgen Now are being rolled out.

The company is also leaning into the broader theme of convergence between technology and life sciences. Griffith described how Amgen is “leveraging AI across the value chain” – from discovery and late‑stage development to manufacturing and customer engagement – as both a productivity lever and a way to handle the complexity of its expanding pipeline.

For investors, the overarching story from Amgen’s 2025 performance is one of transition managed from a position of strength. The company is explicit that some of its biggest legacy revenue streams will shrink. It is equally clear that its future rests not on a single “next big thing” but on a carefully curated cluster: cardiometabolic, rare autoimmune, BiTE oncology, respiratory inflammation and biosimilars. Whether Meritide can deliver on its promise of infrequent, well‑tolerated obesity and diabetes management, and whether opasiran and Repatha can entrench a cardiometabolic franchise that outpaces looming erosion, will determine whether 2026 indeed proves to be a springboard rather than a plateau.