Alnylam Surges on TTR Growth, Margin Pressure Looms

Date of Call: Feb 12, 2026

Financials Results

• Revenue: $3B nearly, up 81% YOY for full year 2025
• Gross Margin: 77% for full year 2025, down 4% YOY

Guidance:

• Combined net product revenue for AMVUTTRA, ONPATTRO, GIVLAARI, and OXLUMO expected to be $4.9B to $5.3B in 2026, representing 71% growth at the midpoint.
• Total TTR revenue expected to be $4.4B to $4.7B, up 83% YOY at the midpoint.
• Collaboration and royalty revenue expected to be $400M to $500M, down 38% YOY at the midpoint.
• Combined non-GAAP R&D and SG&A expense expected to be $2.7B to $2.8B, up 26% YOY at the midpoint.
• U.S. TTR net price expected to decrease mid-single digits in 2026.
• International TTR revenue dollar growth expected to be consistent with 2025.

Business Commentary:

Revenue Growth and Profitability:

• Alnylam Pharmaceuticals achieved nearly $3 billion in combined net product revenues for 2025, representing an 81% increase compared to 2024.
• The company met its profitability goals, achieving GAAP profitability for the full year 2025.
• Growth was driven by the successful launch of AMVUTTRA for ATTR cardiomyopathy and strong performance in the TTR franchise.

TTR Franchise Performance:

• Global TTR net revenues reached $858 million in Q4, up 151% year-over-year.
• In the U.S., TTR franchise revenues grew 222% compared to Q4 2024, driven by increased patient demand.
• The strong performance was attributed to the launch of AMVUTTRA and its established position in the market.

Pipeline and Platform Development:

• Alnylam initiated 3 Phase III studies in 2025 and expanded its clinical pipeline with 4 proprietary CTAs.
• The company developed and launched the siRELIS manufacturing platform, aiming to increase capacity and reduce costs.
• These advancements reflect Alnylam's focus on sustainable innovation and expanding its RNAi therapeutics capabilities.

Guidance and Strategic Goals:

• For 2026, Alnylam provided guidance for combined net product sales of $4.9 billion to $5.3 billion, indicating a 71% growth at the midpoint compared to 2025.
• The company aims to achieve 25% revenue CAGR through 2030 and a non-GAAP operating margin of approximately 30%.
• These targets are supported by strong fundamentals, including improved diagnosis and treatment rates in the ATTR-CM category.

Sentiment Analysis:

Overall Tone: Positive

• Management described 2025 as a 'transformational year' and 'landmark approval' for AMVUTTRA. They 'achieved GAAP profitability' for 2025 and expect to 'sustain profitability going forward'. The company is 'focused firmly on the future' with a '5-year goals' strategy and reiterated strong 2026 revenue guidance, indicating confidence in growth.

Q&A:

• Question from Paul Matteis (Stifel): Could you comment on new patient adds and the mix of first-line for vutrisiran versus tafamidis switches in 2026 and how that's evolving?
  Response: Confidence in guidance is driven by strong fundamentals: improved first-line access, strengthening physician/patient preference, and continued category growth.

• Question from Salveen Richter (Goldman Sachs): Could you speak to the choppiness in Q1 scripts and pricing dynamics for new market entry and growth in Europe?
  Response: Access is strong with most patients having first-line coverage and 0 out-of-pocket costs. 2026 pricing assumes a mid-single-digit net price decrease similar to 2025. Too early for 2027 specifics, but positioned well.

• Question from Konstantinos Biliouris (Oppenheimer): Have you seen seasonality in Q4 that could tailwind Q1 2026?
  Response: Q1 has typical industry seasonality, but underlying category momentum remains robust with 40%+ growth over past several years.

• Question from Ritu Baral (TD Cowen): What is the gross-to-net pattern for 2026 and are access discussions done? Also, are competitive dynamics factoring into gross-to-net?
  Response: 2026 U.S. pricing guidance is a gradual mid-single-digit net price decrease. For 2027, positioned well to manage growth and preserve category value despite potential competition.

• Question from Maurice Raycroft (Jefferies): Can you elaborate on select external innovation in the 30% R&D spend? Should we expect more partnerships like Roche?
  Response: Focused on internal pipeline but open to select external innovation complementary to existing portfolio, with high scientific and financial bars.

• Question from Tazeen Ahmad (Bank of America): How should we think about operating margin impact when nucresiran launches in the early 2030s and patient switching timeline?
  Response: Nucresiran, if successful, has best-in-class profile without royalty obligations, expected to drive operating margins to the mid-40s post-2030.

• Question from Luca Issi (RBC Capital Markets): What are the go/no-go criteria for starting a Phase III trial for Huntington's, given the slowly progressive disease?
  Response: Phase III will be accelerated if Phase I shows >50% durable knockdown of Huntington protein and safety, aiming to bring therapy to patients as quickly as possible.

• Question from Myles Minter (William Blair): What's the rationale for prioritizing ACVR1c over other targets in obesity, and what's the target product profile?
  Response: ACVR1c is prioritized based on preclinical work and emerging peer data suggesting it's a more potent target for weight loss and A1c reduction without GLP-1 side effects.

• Question from Michael Ulz (Morgan Stanley): Do you expect share trends in the front-line setting for cardiomyopathy to continue increasing?
  Response: Confidence in 2026 guidance is supported by continuous progress in first-line access, rising preference, and healthy category growth.

• Question from Edward Tenthoff (Piper Sandler): Should external partnering focus on complementary technology like delivery or other RNA mechanisms?
  Response: Yes, looking at complementary technologies (e.g., delivery) that accelerate internal innovation and expand patient reach.

• Question from Unknown Analyst (Barclays): Which programs in the pipeline are most derisked and most exciting? Also, what is expected for 2027 pricing?
  Response: Most derisked are nucresiran (TTR silencing) and zilebesiran (blood pressure). 2027 pricing is expected to follow the same gradual mid-single-digit net price decrease trend as 2025-2026.

Contradiction Point 1

U.S. Net Price Decline Outlook

Guidance on the pattern of U.S. net price decrease shifts from a gradual trend to a specific stepwise avoidance.

What are your thoughts on the current market trends impacting your business? - Ritu Baral (TD Cowen)

20260212-2025 Q4: The mid-single-digit net price decrease in the U.S. is expected to be gradual throughout 2026, not a stepwise adjustment in Q1. - [Jeffrey Poulton](CFO)

For 2026, is the mid-single-digit gross-to-net decline stepwise or gradual? Are access discussions finalized, and are competitive dynamics considered in pricing? - Maurice Raycroft (Jefferies LLC, Research Division)

2025Q3: For the full year, a mid-single-digit net price decline is expected for the TTR franchise. - [Jeffrey Poulton](CFO)

Contradiction Point 2

European Market Launch Timing

The timeline for a broader ex-U.S. launch shifts from mid-2026 to an expectation of matching 2025 growth in 2026.

What are your thoughts on the recent market volatility? - Salveen Richter (Goldman Sachs)

20260212-2025 Q4: International TTR revenue growth is expected to match 2025 in 2026, with a Q1 headwind from adjusted pricing in Germany. - [Tolga Tanguler](EVP)

How did Q1 script volatility, pricing strategies for new markets, and growth trends in Europe impact performance? - Maurice Raycroft (Jefferies LLC, Research Division)

2025Q3: The broader ex-U.S. launch is expected in mid- to late 2026. - [Tolga Tanguler](EVP)

Contradiction Point 3

Patient Uptake and Prescriber Mix

Contradiction on whether uptake is balanced or initially stronger in a specific patient segment.

What are your key growth strategies for the next fiscal quarter? - Paul Matteis (Stifel)

20260212-2025 Q4: Early uptake was faster among stabilizer progressors, but utilization has now become relatively balanced between first-line, new starts and stabilizer progressors. - [Yvonne Greenstreet](CEO)

How do you see new patient adds and the first-line treatment mix of vutrisiran versus tafamidis switches evolving by 2026? - Salveen Jaswal Richter (Goldman Sachs Group, Inc.)

2025Q2: The launch is off to a strong start with broad and robust uptake... Early uptake was faster among stabilizer progressors, but utilization has now become relatively balanced... - [Yvonne Greenstreet](CEO)

Contradiction Point 4

Pricing Guidance

Contradiction on the characterization of pricing dynamics and patient out-of-pocket costs.

What is the question from Salveen Richter of Goldman Sachs? - Salveen Richter (Goldman Sachs)

20260212-2025 Q4: Out-of-pocket costs are minimal... Net price decreased mid-single digits in 2025, with a similar mid-single-digit decline expected in 2026. - [Tolga Tanguler](CCO)

How did Q1 script volatility, pricing for new markets, and European growth trends impact performance? - Tazeen Ahmad (BofA Securities)

2025Q2: Payer dynamics are moving as expected, with broad first-line coverage and minimal out-of-pocket costs for patients (often zero). - [Tolga Tanguler](CCO)

Contradiction Point 5

U.S. Net Price Decrease Expectation for 2026

Inconsistent guidance on the magnitude of the U.S. net price decrease for 2026.

What are your key priorities for the upcoming quarter? - Salveen Richter (Goldman Sachs)

20260212-2025 Q4: Net price decreased mid-single digits in 2025, with a similar mid-single-digit decline expected in 2026. - [Tolga Tanguler](CCO)

Could you discuss Q1 script volatility, pricing strategies for new markets, and growth trends in Europe? - Ellie Merle (UBS)

2025Q1: There is no price difference between the PN and CM indications. - [Tolga Tanguler](CCO)