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Eyes on Alnylam
- Jana Chisholm
- 9 hours ago
- 3 min read
Alnylam posted its first-ever GAAP profit in 2025, reporting $314 million in net income. Amvuttra’s rapid ATTR-CM expansion drove the turnaround, though Q4 sales modestly missed expectations. Meanwhile, competitive pressure from Pfizer and BridgeBio is reshaping the ATTR-CM landscape. and pricing dynamics and early-year volatility may weigh on near-term performance despite strong full-year guidance.
Alnylam's Long Road to Profitability
For the first time in its history, Alnylam Pharmaceuticals reported a full-year GAAP profit. After 23 years of RNA interference research and commercialization efforts, the company generated $314 million in net income in 2025, reversing a $278 million loss in 2024.
The milestone reflects the maturation of Alnylam’s transthyretin (TTR) franchise, particularly the continued expansion of Amvuttra in transthyretin amyloid cardiomyopathy (ATTR-CM).
Amvuttra: Strong Growth, Slight Miss
At the J.P. Morgan Healthcare Conference, Alnylam disclosed preliminary fourth-quarter Amvuttra sales of $827 million. While strong, the figure fell roughly 3% below analyst expectations following two consecutive quarterly beats earlier in the launch.
Investor reaction was swift. Shares have declined nearly 19% over the past month, erasing gains seen after the company’s first ATTR-CM launch update in July 2025.
Management remains confident. The company projects total TTR franchise revenue of $4.4 billion to $4.7 billion in 2026 — representing approximately 83% growth year over year at the midpoint.
Short-Term Volatility Ahead
Despite strong annual guidance, CFO Jeff Poulton cautioned that the first quarter could be “very disappointing” due to several temporary factors:
Annual insurance resets early in the year
Fewer shipping weeks in Q1 compared with Q4
International pricing adjustments, particularly in Germany
Germany’s price reduction is expected to reduce revenue by approximately $25 million this quarter. However, the company views the move as strategically necessary to compete effectively in the country’s larger cardiomyopathy market.
Management expects stronger quarterly growth later in 2026 across both U.S. and international markets.
Pricing Pressure and Market Share Dynamics
Alnylam anticipates a mid-single-digit decline in Amvuttra’s U.S. net price in 2026. While not unexpected in specialty cardiology markets, it highlights increasing competitive intensity.
As of September, Amvuttra captured 27% of first-line new patient starts in the U.S., compared with 51% for Pfizer’s Vyndamax. More than 90% of payers now provide first-line coverage for Amvuttra, limiting step-edit barriers.
The broader ATTR-CM market is evolving rapidly. In addition to Pfizer and Alnylam, BridgeBio Pharma markets Attruby (acoramidis), whose clinical data have raised expectations for category expansion.
However, analysts remain uncertain how much additional patient penetration the market can sustain. Competitive growth is already affecting Pfizer: Vyndamax U.S. sales declined 7% year over year in Q4, falling from $948 million in Q3 to $910 million.
Patent Uncertainty Adds Complexity
Another overhang is the long-term durability of tafamidis. BridgeBio shares fell 15% after Pfizer withdrew a tafamidis polymorph patent in the EU. Pfizer now believes tafamidis patent protection could expire by the end of 2028. Generic timing could materially reshape ATTR-CM pricing and access dynamics over the next several years.
Outlook: Category Growth vs. Competitive Compression
Alnylam argues the category continues to expand, supported by increasing physician familiarity and patient identification. The company believes growth in newly diagnosed patients will offset competitive share shifts.
The central question for investors is no longer whether Alnylam can scale its RNAi platform — it has demonstrated that. Instead, attention is turning to:
How durable pricing will be
How much incremental patient growth remains
And how ATTR-CM competition evolves ahead of potential generic disruption
After finally reaching profitability, Alnylam now faces a different challenge: defending growth in a rapidly crowding market.
