Alnylam Q3 Product Revenue Jumps 52% on AMVUTTRA Growth

Alnylam Pharmaceuticals reported a 52% year-over-year increase in third-quarter 2026 net product revenue, driven by continued expansion of its transthyretin amyloidosis franchise following the ATTR cardiomyopathy launch of AMVUTTRA. The company reiterated its full-year product revenue guidance while expanding enrollment in a pivotal study of next-generation TTR therapy nucresiran.

Total net product revenue reached $1.29 billion, up from $851 million a year earlier and 10% from the second quarter. At constant exchange rates, product revenue increased 53% year over year. Total revenue rose 17% to $1.46 billion as lower collaboration revenue partly offset product growth.

TTR franchise leads product growth

Global TTR product revenue from AMVUTTRA and ONPATTRO increased 59% year over year and 12% sequentially to $1.15 billion. U.S. TTR revenue rose 69% from the prior-year quarter and 12% from the second quarter, while revenue outside the U.S. increased 28% year over year and 10% sequentially.

Alnylam attributed the annual U.S. increase to strong demand following AMVUTTRA’s ATTR-CM launch, partly offset by a lower net price. Compared with the second quarter, U.S. TTR revenue benefited from $81 million of demand growth, a $17 million inventory benefit and about $10 million of favorable one-time gross-to-net adjustments. Ending U.S. inventory increased to 21 days from 19 days in the second quarter.

Outside the U.S., year-over-year growth primarily reflected ATTR-CM uptake in Japan and Germany, partly offset by lower cardiomyopathy pricing in launch markets. Sequential growth was supported by ongoing launches in Germany, Italy and Japan, as well as the timing of orders in partner markets.

The company said U.S. ATTR-CM prescription volume grew about 37% from the third quarter of 2025 and roughly 70% since March 2025. AMVUTTRA held an approximately 24% share of total prescriptions across ATTR polyneuropathy and cardiomyopathy through the third quarter. More than 2,000 new prescribers have used the medicine since March 2025, with utilization spanning centers of excellence and community settings.

Alnylam estimated that about 80% of ATTR-CM patients remain untreated. It also said AMVUTTRA is accessible to approximately 99% of covered lives, with the large majority receiving first-line access, and that about 90% of patients can obtain treatment within roughly 10 miles of home.

The rare-disease franchise generated $142 million in quarterly revenue, up 12% year over year and unchanged sequentially. GIVLAARI revenue rose 21%, primarily due to an increase in patients receiving therapy and the timing of partner-market orders. OXLUMO revenue declined 1% as patient growth was offset by a lower net price and order timing.

Operating margin narrows as spending increases

Net revenue from collaborations and royalties fell 58% to $166 million. Collaboration revenue declined 80% to $71 million, while royalty revenue more than doubled to $95 million.

Gross margin on product revenue decreased to 72% from 77% a year earlier, and gross margin on total revenue fell to 75% from 84%. Non-GAAP combined research and development and selling, general and administrative expenses increased 17% to $671 million. R&D spending rose 21% to $376 million, while SG&A expense increased 13% to $296 million.

Non-GAAP operating income declined 11% to $425 million, and the corresponding operating margin narrowed to 29% from 38%. Cash, cash equivalents and marketable securities totaled $3.59 billion at quarter-end, compared with $2.91 billion at the end of 2025.

Full-year guidance reaffirmed

Alnylam maintained its 2026 total net product revenue forecast of $4.7 billion to $5.1 billion, representing reported growth of 57% to 71% from 2025. The company expects TTR product revenue of $4.2 billion to $4.5 billion and rare-disease product revenue of $500 million to $600 million.

Management also reiterated guidance for $575 million to $625 million of collaboration and royalty revenue and $2.7 billion to $2.8 billion of combined non-GAAP R&D and SG&A expenses. The expense measure excludes an estimated $330 million to $380 million of stock-based compensation.

Nucresiran study expands; Huntington’s program advances

Alnylam increased the planned enrollment of the Phase 3 TRITON-CM trial of nucresiran to approximately 2,250 patients from about 1,750. The event-driven study uses a primary composite endpoint of all-cause mortality and recurrent cardiovascular events. According to the company, the larger enrollment is intended to preserve statistical power under conservative outcome-event assumptions and further enrich the study for patients with earlier disease. Alnylam said the expected launch timeline, subject to successful development and regulatory approval, remains by 2030.

The company also presented initial Phase 1 results for brezosiran, an investigational Huntington’s disease therapy developed with Regeneron. A single intrathecal dose produced a dose-dependent reduction in cerebrospinal-fluid mutant huntingtin, including a mean reduction of up to 64% at month three and individual reductions of up to about 80%. Alnylam described the observed safety and tolerability profile as encouraging and is continuing a Phase 1b open-label extension with repeat dosing every six months.

Pending alignment with regulators, the company plans to begin a placebo-controlled pivotal trial of brezosiran in adults with Huntington’s disease in 2027. The study is intended to evaluate whether the therapy can slow disease progression.

Potential changes to the U.S. 340B Drug Pricing Program remain an access risk. Alnylam said a proposed rule could reduce hospital outpatient reimbursement for Part B medicines acquired by 340B institutions beginning January 1, 2027, if implemented. The company is considering contracting with health systems and enabling alternative sites of care to mitigate possible access disruptions.

Other uncertainties identified by Alnylam include clinical and regulatory outcomes, pricing and reimbursement, manufacturing and supply, intellectual-property protection, reliance on partners and third parties, litigation, and the company’s ability to manage growth and operating expenses.