Alnylam Adjusts 2025 TTR Guidance to $4.2B-$4.5B Due to Patient Mix Changes

Alnylam Pharmaceuticals has recalibrated its 2025 revenue guidance for its transthyretin-mediated (TTR) amyloidosis franchise to a range of $4.2 billion to $4.5 billion. This adjustment lowers the midpoint by $200 million, reflecting a normalization in patient demographics as the company moves past its initial launch phase.

The updated outlook follows a period of commercial expansion for AMVUTTRA, the company's RNAi therapeutic. Management attributed the guidance revision to a shift in patient mix. The patient base has transitioned from a more balanced split during the launch period to approximately 80% first-line patients and 20% second-line patients.

"In Q2 this year, we crossed $1 billion of revenue in just one quarter. I think that’s particularly impressive given that we achieved the cardiomyopathy indication in March of 2025," said Yvonne Greenstreet, Chief Executive, Alnylam Pharmaceuticals, in a statement at the Morgan Stanley conference.

Commercial Momentum and Market Penetration

Alnylam continues to report adoption rates among specialists. Greenstreet highlighted that the company currently maintains a greater than 50% market share among physicians who have utilized AMVUTTRA for treatment.

This growth is supported by the March 2025 approval of AMVUTTRA for the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis. The expansion into the cardiomyopathy indication has been a driver for the company's recent quarterly revenue milestones.

Financial Context and Market Valuation

Alnylam Pharmaceuticals (ALNY) stock was trading at $242.07 as of September 16, 2026. The company's TTR franchise remains its revenue generator, and the shift toward a predominately first-line patient base suggests a transition from early-adopter growth to a long-term commercial model.

For investors and market analysts, the core question is how effectively the company can maintain its market share as it shifts focus toward broader first-line adoption. The current guidance reflects a strategic recalibration, balancing the reality of a changing patient mix with the commercial momentum observed in the first half of the year.