Alnylam Pharmaceuticals, Inc. Q4 FY2025 earnings call

• Alnylam possesses a unique profile in the biotech industry with an established innovation engine and commercial excellence. In 2025, the company achieved a landmark approval of Amvuttra for ATTR cardiomyopathy, delivering nearly $3 billion in combined net product revenues, an 81% growth compared to 2024, and achieved GAAP profitability for the full year.
• On the commercial front, the TTR franchise had robust performance in Q4 2025, with global TTR net revenues showing significant growth. The rare disease franchise also continued to deliver meaningful impact, with GIVLAARI and OXLUMO growing to a $500 million franchise in 2025.
• Pipeline and platform updates: In 2025, Alnylam initiated three Phase 3 studies, expanded its clinical pipeline with new programs, and launched the Cyrillis enzymatic ligation-based RNAi manufacturing platform. The company also shared its five-year goals, Alnylam 2030, with strategic pillars including achieving global TTR leadership, growing through sustainable innovation, and scaling with discipline and agility to drive profitable growth.

In Q4 2025, global TTR net revenues reached $858 million, up 18% versus the prior quarter and 151% year over year. The rare disease franchise generated $136 million in net revenue in Q4, up 26% versus the same period last year. For the full year 2025, total global net product revenues were nearly $3 billion, an 81% growth versus 2024, driven by the strong performance of the TTR franchise, particularly the launch of Amvuttra in ATTR cardiomyopathy. The TTR franchise contributed significantly to the revenue growth, with its net revenues more than doubling compared to 2024. The rare disease franchise also showed consistent growth, with GIVLAARI and OXLUMO together becoming a $500 million franchise in 2025.

• Net product revenues: Anticipate combined net product sales for four commercial products to be within $4.9 billion to $5.3 billion in 2026, representing a 71% growth at the midpoint of the range compared to 2025. Total TTR franchise guidance is $4.4 billion to $4.7 billion.
• Collaboration and royalty revenue: Guidance range is $400 million to $500 million, a decrease from 2025 due to the non-recurrence of the one-time zalesiran development milestone.
• Non-GAAP R&D and SG&A expense: Guidance range is $2.7 billion to $2.8 billion, representing a 26% growth versus 2025, driven by increased investments in clinical studies and launch activities.

Q: Could you comment on what is seen so far in 2026 in terms of new patient adds and the mix of first line for vutrisiran versus tafamidis switches?

A: Yvonne and Tolga responded that they are pleased with the Amvuttra launch, highlighting the strong fundamentals and continued growth trends which support the guidance.

Q: Speak to the choppiness in the first quarter for the TTR franchise and pricing dynamics as well as growth dynamics in Europe?

A: Tolga responded that Alnylam is well positioned from an access standpoint, with a large majority of patients having first-line access, and net price is expected to decline mid-single digits in 2026 as the business scales.

Q: Have you seen any seasonality during the fourth quarter potentially affecting 2026?

A: Tolga responded that while there may be some seasonality, the longer-term category trend has been robust and well-sustained growth, and seasonality is not impacting the underlying momentum.

Q: Comment on the gross-to-net pattern over 2026 and potential longer-term competitive dynamics?

A: Jeffrey responded that the net price decrease in 2026 is expected to be gradual, and Tolga added that Alnylam is well positioned to manage growth and preserve category value despite potential competition.

Q: Elaborate on select external innovation as part of the approximate 30% revenue R&D spend?

A: Yvonne responded that Alnylam is focused on its internal pipeline but is open to select external innovation that complements its existing portfolio and R&D pipeline, with a high science and financial bar.

Q: Impact of nuceresiran on operating margin once available?

A: Yvonne and Jeffrey responded that nuceresiran, if successful, would have a best-in-class profile leading to swift patient uptake and potentially driving operating margins to the mid-40s post 2030, with no royalty obligations for nuceresiran.

Q: Walk through the go/no-go decision to start a Phase 3 trial for Huntington’s?

A: Pushkal responded that the Huntington’s program is being evaluated based on achieving good levels of huntingtin knockdown and safety, with plans to accelerate if positive data is obtained.

Q: Rationale for prioritizing ACVR1C asset over INHBE in obesity program?

A: Pushkal responded that ACVR1C is prioritized due to preclinical data suggesting it is a more potent target compared to INHBE, with expectations of sharing results later in the year.

Q: Trends in cardiomyopathy market share and whether share trends will continue to increase?

A: Tolga responded that Alnylam is seeing positive trends in market share, with progress in first-line access and healthy category growth supporting the outlook for 2026.

Q: Thoughts on external partnering and complementary technology?

A: Yvonne and Pushkal responded that Alnylam is looking for external innovation that is complementary to its internal pipeline and current portfolio, focusing on technology areas that help accelerate innovation and bring medicines to more patients.

Q: Most excited early-stage pipeline programs and expectations for 2027 pricing?

A: Pushkal responded that programs like nuceresiran, zalesiran, and the plasminogen program are exciting, with expected de-risking data in 2026 and 2027. Jeffrey responded that pricing in 2027 is expected to follow a similar gradual net price decrease trend as seen in 2026, consistent with the long-term growth strategy.

Q: Views on competitive silencer data impact on Amvuttra?

A: Pushkal and Tolga responded that it is premature to speculate, but additional entrants will help expand the category, and Alnylam is well positioned with its own strong clinical data package and dosing profile.

Q: Sense of Amvuttra access in community centers?

A: Tolga responded that Alnylam is well positioned from an access standpoint, with a large majority of patients having first-line access within 10 miles of their homes, and continuing to expand the network of sites of care.