Tafamidis

Alnylam's shares are under pressure as Amvuttra's Q4 sales missed high expectations and the company offered a few caveats for 2026. Alnylam Pharmaceuticals achieved profitability for the first time in its history in 2025.After 23 years of investing in R&D and launching new products, the company reported a net income by GAAP of $314 million for the full year of 2025, compared with a loss of $278 million in 2024.The RNA interference specialist expects to sustain profitability going forward, CEO Yvonne Greenstreet said on the company’s fourth-quarter earnings call Thursday.The shift to profitability was driven by the rapid growth of Alnylam’s transthyretin franchise, particularly Amvuttra for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM).However, Amvuttra’s Q4 sales of $827 million, which Alnylam preliminarily announced in January at the J.P. Morgan Healthcare Conference, came about 3% below analysts’ expectations, which had risen after two consecutive beats in the first two quarters of the drug’s ATTR-CM launch.Alnylam’s shares have dropped about 19% in the past month—including a 6% decline Thursday as of publication time—more than erasing the gains rallied since the company’s first ATTR-CM launch quarterly report in late July 2025.For 2026, Alnylam’s guidance on product revenues for its TTR franchise—between $4.4 billion and $4.7 billion—represents 83% growth compared with 2025 at the midpoint.  But the company expects to see some nuanced turbulence in the TTR business, which includes both Amvuttra and Onpattro.Specifically, Alnylam expects a mid-single-digit net price decrease for Amvuttra in the U.S. this year. Meanwhile, the first quarter may prove particularly underwhelming, and for a variety of reasons, according to Alnylam CFO Jeff Poulton.There’s the typical impact of annual insurance reset at the beginning of the year, he said. Second, Alnylam expects “more modest quarter-over-quarter” TTR growth in Q1 2026 compared with the $111 million U.S. quarterly growth achieved in Q4 2025, thanks to “fewer product shipping weeks,” Poulton explained on the call.Outside of the U.S., international markets contributed $23 million in Q4 quarterly growth, but the company anticipates a roughly $25 million reduction this quarter thanks to price cuts in Germany. The price concession is important as it positions Alnylam “to compete effectively and participate in the substantially larger CM market in Germany,” Alnylam’s chief commercial officer, Tolga Tanguler, said on the call.For both markets, higher quarterly growth is expected for the remainder of the year, Poulton said.Early launch metrics have given Alnylam confidence in Amvuttra’s future growth. The drug is gaining first-line share in new patient starts, reaching 27% in the U.S. as of September, compared with 51% for Pfizer’s first-to-market Vyndamax (tafamidis).“Establishing Amvuttra as a first-line option remains our strategic priority, and we’re making meaningful progress,” Tanguler said.Over 90% of payers now provide first-line coverage with “the large majority” of patients able to initiate treatment without step-edits requirements, Tanguler said, citing 2026 payer policy discussions.Industry watchers are closely following the ATTR-CM space. Besides Alnylam and Pfizer, BridgeBio sells Attruby (acoramidis), whose strong performance has also contributed to increased optimism in ATTR-CM.However, questions about the growth potential of the ATTR-CM market remain, as analysts wonder just how many more patients the drugmakers can reach. Already, the growth of Amvuttra and Attruby is coming at the cost of Pfizer’s Vyndamx, which reported a 7% year-over-year U.S. sales decline to $910 million in Q4, compared with $948 million in Q3.Unlike in previous quarters, Alnylam management on Thursday’s call didn’t provide specific numbers on new patients added to Amvuttra’s brand.“We’re clearly seeing a strengthening physician and patient preference, and even more importantly, continued category growth with more patients entering the market,” Tanguler said. Meanwhile, the timing of Vyndamx's genericization remains a key focus for the field. News of Pfizer’s withdrawal of a tafamidis polymorph patent in the EU caused a 15% decline in BridgeBio’s stock price last week.Right now, Pfizer assumes that tafamidis will lose patent protection at the end of 2028, CEO Albert Bourla said on the company’s Q4 earnings call last week. He declined to offer further comments because “these are very sensitive topics.”

With more than 100 ongoing phase 3 trials and over 20 late-stage readouts slated for 2026, AstraZeneca is entering an “unprecedented catalyst-rich period,” CEO Pascal Soriot said. After ending 2025 with a strong fourth quarter, AstraZeneca management has doubled down on its ambitious “$80 billion by 2030” revenue target, outlining a roadmap to have more than 25 blockbuster medicines by the end of the decade.During AZ’s Q4 earnings call, CEO Pascal Soriot highlighted an “unprecedented catalyst-rich period.” With more than 100 ongoing phase 3 trials and over 20 late-stage readouts slated for 2026, AZ’s exec team used a big chunk of their time on the call taking inventory of key clinical programs.That large portfolio shows the value of diversification, again highlighting what Soriot called “low concentration risk.”“It’s great to have one or two big products. [It] makes you very profitable and makes you look good,” Soriot said. “But if you lose one of those, as we’ve seen happen to some actors in the industry lately, it really becomes very painful, very quickly. So this diversification, both product-wise, but also geographically, is suddenly becoming more apparent as we drive growth through therapy areas but also through regions.”AZ capped 2025 with fourth-quarter revenues of $15.5 billion, which arrived slightly above analysts’ expectations, thanks mainly to the company's oncology portfolio.But rather than commercial performance, analysts on Tuesday’s call were heavily focused on AZ’s clinical programs, wondering whether the British pharma can repeat the level of phase 3 successes it enjoyed last year.Among key 2026 readouts at the top of AZ’s—and investors’—minds are: Avanzar evaluating Daiichi Sankyo-partnered Datroway in first-line non-small cell lung cancer; Serena-4 for the oral SERD camizestrant in first-line HR-positive breast cancer; CardioTTRansform testing Ionis-partnered Wainua in transthyretin amyloid cardiomyopathy; three phase 3 trials of efzimfotase alpha in the rare metabolic bone disease hypophosphatasia; and three phase 3 studies of the IL-33 agent tozorakimab in chronic obstructive pulmonary disease (COPD). Avanzar represents the epitome of AZ’s recent efforts to help improve the probability of success of its clinical studies. With the help of artificial intelligence, the company developed a new TROP2-based biomarker in the hopes of enriching for responders to Datroway. In April 2025, AZ signed a three-way deal with Tempus AI and Pathos AI to construct a patient data-based multimodal oncology model.“My reflection of the last decade in oncology, about the success rates we’ve had, has been predicated on being able to identify the right patient populations to treat,” AZ’s oncology R&D head, Susan Galbraith, Ph.D., said on Tuesday’s call.AZ has been using real-world evidence to help design its phase 3 trials and predict control-arm performance. The hope is that AI models can help in the same way when historical literature data are lacking in certain new biomarker areas or where the biology is more complicated, Galbraith said.As for camizestrant, industry watchers are eager to see results from AZ’s first-line Serena-4 trial and the phase 3 Cambria-1 and -2 studies in early breast cancer, after Roche reported positive data for its rival oral SERD, giredestrant, in two similar settings. The key focus is if oral SERDs can break into an earlier and larger population beyond patients whose tumors have ESR1 mutations.For the first-line trial, AZ has designed the study to enrich for endocrine-sensitive patients, who are expected to respond better to oral SERDs, Galbraith said. Those patients typically experienced recurrence from early-stage disease after at least two years of standard adjuvant therapy because those that are less endocrine-sensitive typically progress more rapidly, she explained.In the adjuvant setting, the two studies target different patient populations that could potentially give AZ access to the largest group of patients, Galbraith said. While Cambria-1 allows patients to have used a CDK4/6 inhibitor, Cambria-2 allows concurrent use of a CDK4/6 inhibitor, which Galbraith said is important now that these meds are becoming the new standard in the adjuvant setting.Outside of oncology, as one analyst noted on Tuesday’s call, AZ has billed efzimfotase alpha as having the opportunity to reach $3 billion to $5 billion in peak sales. The drug’s once-every-other-week dosing is considered an upgrade from the up to once-every-two-days frequency of AZ’s Strensiq.With three phase 3 trials, AZ’s goal is again for the newer enzyme therapy to reach a broad population, Marc Dunoyer, CEO of AZ’s rare disease unit, Alexion, said on the call. Two trials are in the pediatric population—one in which patients switch from Strensiq and the other in Strensiq-naïve patients—and the third trial combines adolescents and adults.In the biopharmaceutical department, AZ is targeting the very competitive ATTR-CM field. As the largest trial in this disease, CardioTTRansform is powered to run a key subgroup analysis among patients who are on baseline treatment with Pfizer’s Vyndamax. Information here is important because it may change treatment guidelines, Sharon Barr, Ph.D., AZ’s head of biopharmaceuticals R&D, said on the call. A big question for AZ’s biopharmaceutical business is whether the company can sustain the blow from the loss of exclusivity of its SGLT-2 inhibitor Farxiga, which generated $8.4 billion in sales in 2025. The drug was also one of the first drugs selected for price negotiations under the Inflation Reduction Act, with a discount for Medicare taking effect at the beginning of this year.AZ’s biopharmaceutical business will “have a blip” following the Farxiga patent cliff, but the company has enough other growth drivers, Ruud Dobber, who leads the unit, said on the call.He pointed to the potential 2026 launch of baxdrostat for hard-to-control hypertension, noting that AZ has set the drug’s overall peak sales potential above $5 billion. Respiratory and immunology drugs Breztri and Tezspire are also expected to continue their double-digit growth, he said.