Alnylam Pharmaceuticals reported that quarterly AMVUTTRA revenue surpassed $1 billion as the RNA interference therapeutics company delivered substantial revenue growth and swung to profitability. However, management reduced its full-year product revenue outlook after demand among certain second-line patients normalized following an initial launch period boosted by pent-up demand.
AMVUTTRA generated $1.01 billion in global net product revenue during the second quarter of 2026, increasing 106% from $492 million in the prior-year period. The treatment accounted for the majority of Alnylam’s $1.17 billion in total quarterly product revenue.
AMVUTTRA and ONPATTRO produced combined transthyretin, or TTR, product revenue of $1.03 billion, representing an 89% increase from $544 million a year earlier. ONPATTRO revenue declined 65% to approximately $18 million as the company continued transitioning its TTR franchise toward AMVUTTRA.
AMVUTTRA is approved for adults with hereditary transthyretin-mediated amyloidosis with polyneuropathy and for adults with wild-type or hereditary transthyretin-mediated amyloidosis with cardiomyopathy. The treatment is administered through a quarterly subcutaneous injection.
The company said U.S. TTR product revenue increased by $106 million compared with the first quarter. Demand contributed a $129 million sequential increase, which was partly offset by approximately $20 million of inventory effects and a modest reduction in net pricing.
Alnylam said the increase in U.S. demand during the quarter was more than twice the demand growth recorded between the fourth quarter of 2025 and the first quarter of 2026. International TTR revenue increased by another $14 million sequentially as demand grew across cardiomyopathy and polyneuropathy markets.
Despite that quarterly acceleration, Alnylam reduced its expected full-year 2026 TTR product revenue range from $4.4 billion to $4.7 billion to $4.2 billion to $4.5 billion.
The company attributed the revision to an updated outlook for AMVUTTRA among second-line patients in the U.S. cardiomyopathy market. Early demand from patients progressing while receiving stabilizer treatments had been stronger than management initially recognized.
Alnylam said many of those patients had been waiting for a new therapeutic option, creating pent-up demand during the early phase of the AMVUTTRA launch. Second-line demand growth moderated during early 2026 to what the company now considers a normalized level.
The updated midpoint still implies approximately 75% TTR revenue growth compared with 2025, indicating that management continues to expect substantial expansion despite lowering its expectations.
Alnylam also reduced its total net product revenue guidance from between $4.9 billion and $5.3 billion to between $4.7 billion and $5.1 billion. Expected product revenue growth was revised to between 57% and 71%, compared with the previous range of 64% to 77%.
The lower product outlook was partly offset by increased expectations for collaboration and royalty revenue. Alnylam raised that guidance from between $400 million and $500 million to between $575 million and $625 million.
Royalty revenue increased 79% to approximately $72 million during the second quarter, primarily because of increased global Leqvio sales by Novartis and a higher applicable royalty rate.
Collaboration revenue declined 23% to $47 million. Lower revenue recognized through Alnylam’s collaboration with Regeneron was partly offset by higher Roche collaboration revenue associated with reimbursable development activities for the Phase 3 ZENITH study of zilebesiran.
Total second-quarter revenue increased 67% to $1.29 billion from $774 million. The company generated GAAP operating income of $231 million, compared with an operating loss of $16 million in the prior-year quarter.
Non-GAAP operating income increased to $318 million from $95 million. Alnylam also reported GAAP net income of $164 million, or $1.21 per diluted share, compared with a net loss of $72 million, or $0.55 per share.
Non-GAAP net income reached $252 million, or $1.84 per diluted share, compared with $38 million, or $0.28 per diluted share, in the second quarter of 2025.
Alnylam’s rare-disease medicines also delivered growth. GIVLAARI revenue increased 11% to approximately $90 million, while OXLUMO revenue rose 11% to approximately $52 million. Combined rare-disease product revenue increased 11% to $142 million.
Higher AMVUTTRA sales also increased the company’s royalty expenses. Cost of goods sold more than doubled to $298 million, increasing from 21.1% to 25.4% of product revenue.
Alnylam attributed the higher cost ratio primarily to increased AMVUTTRA revenue and a corresponding increase in the blended royalty rate payable on the treatment’s sales.
GAAP research and development expenses increased 28% to $413 million, while non-GAAP research and development expenses rose 38% to $377 million. The increase reflected higher clinical trial spending for zilebesiran and nucresiran programs.
GAAP selling, general, and administrative expenses increased 8% to $348 million. Non-GAAP expenses rose 14% to $297 million as Alnylam increased marketing investments supporting AMVUTTRA’s global cardiomyopathy launch.
The company maintained its full-year non-GAAP research and development and selling, general, and administrative expense guidance of between $2.7 billion and $2.8 billion.
Alnylam ended the quarter with $3.3 billion in cash, cash equivalents, and marketable securities, compared with $2.9 billion at the end of 2025. The increase was primarily driven by cash generated through operating activities.
The company also expanded AMVUTTRA’s international reach by launching the treatment in Spain and entering an exclusive agreement with BeOne Medicines for commercialization in mainland China and Macao, subject to regulatory approval.
Beyond AMVUTTRA, Alnylam initiated Phase 2 studies involving ALN-6400 in von Willebrand disease and mivelsiran in Down syndrome-associated Alzheimer’s disease. The company also plans to present initial clinical results for ALN-HTT02 in Huntington’s disease in October 2026.
The quarter highlights the unusual position Alnylam now occupies. Its lead product more than doubled revenue, total company revenue increased 67%, and the business swung from losses to profitability. Yet management reduced guidance because the strongest phase of pent-up second-line demand appears to have passed.
KEY QUOTES:
“During the first half of 2026, we continued to meaningfully advance our business, generating over $1 billion in quarterly product revenues for the first time in our history during the first quarter and, building on that momentum, over $1 billion in TTR revenues during the second quarter. These results underscore the growing leadership and global impact of our TTR franchise in transforming outcomes for patients with ATTR amyloidosis, with AMVUTTRA being the only product approved for the full spectrum of the disease. We have lowered our TTR product sales guidance for full-year 2026 to reflect learnings from the initial phase of our launch in the evolving ATTR-CM market, in particular the normalization of growth in second line volume after satisfying pent-up demand from patients waiting for a new therapy. Given the strong foundation we have established and continued growth in ATTR-CM diagnosis and treatment, we remain confident in the trajectory of our ongoing ATTR-CM launch and are continuing to invest robustly in this franchise, as we bring AMVUTTRA to more patients and establish it as a foundational therapy. During the second quarter, we also continued to advance our high-value pipeline with the initiation of two Phase 2 studies, ALN-6400 in von Willebrand disease and mivelsiran in Down syndrome-associated Alzheimer’s disease, while progressing multiple additional programs toward important clinical readouts later this year. Together, these achievements demonstrate our continued progress against our Alnylam 2030 strategy and our commitment to creating long-term value through scientific innovation and patient impact.”
Yvonne Greenstreet, M.D., Chief Executive Officer of Alnylam
