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.”