Alnylam Pharmaceuticals (NASDAQ:ALNY) reported second-quarter 2026 global net product revenue of approximately $1.2 billion, up 74% from a year earlier, driven by continued uptake of AMVUTTRA for transthyretin amyloidosis with cardiomyopathy, or ATTR-CM.
Chief Executive Officer Yvonne Greenstreet said the quarter marked the first time AMVUTTRA revenue exceeded $1 billion in a single quarter. The company said the result represents an annualized revenue run rate of more than $4 billion about 15 months after the ATTR-CM launch.
Revenue Growth and Updated Guidance
Chief Financial Officer Jeff Poulton said total TTR net revenue reached $1.03 billion during the second quarter, increasing 13% sequentially and 89% year over year. Combined net product revenue was $1.17 billion, while rare disease portfolio revenue totaled $142 million, up 11% from the prior-year period.
Alnylam revised its 2026 total net product revenue guidance to a range of $4.7 billion to $5.1 billion. TTR revenue guidance was reduced to $4.2 billion to $4.5 billion, a $200 million reduction at the midpoint from the company’s prior outlook. The revised range still implies 75% annual TTR revenue growth at the midpoint, Poulton said.
The company raised its outlook for collaboration and royalty revenue to $575 million to $625 million, representing a $150 million increase at the midpoint. Poulton attributed the increase largely to higher royalties from Novartis’ LEQVIO sales and greater cost reimbursement from Roche related to enrollment in the ZENITH Phase III trial of zilebesiran.
For the quarter, collaboration revenue declined 23% year over year to $47 million, while royalty revenue rose 79% to $72 million. Alnylam reported non-GAAP operating income of $318 million, more than triple the prior-year amount, and ended the quarter with $3.3 billion in cash, cash equivalents and marketable securities.
First-Line Demand Becomes Central Focus
Chief Commercial Officer Tolga Tanguler said approximately 80% of new treatment initiations in the ATTR-CM category are now first-line starts. The company views this segment as the larger and more durable growth opportunity, while second-line demand from patients previously treated with stabilizers has moved toward what management described as a sustainable underlying rate.
In the U.S., TTR revenue increased 15% sequentially and 114% year over year. Underlying demand increased by $129 million during the quarter, though reported growth was reduced by $21 million due to inventory changes, Tanguler said. Outside the U.S., TTR revenue grew 7% sequentially and 31% year over year, supported by ATTR-CM uptake in Japan, the U.K. and Germany and polyneuropathy performance in international markets.
Management said AMVUTTRA access remains broad and adherence exceeds 90%. Since the ATTR-CM launch, Alnylam has added more than 1,700 prescribers, though Tanguler said the company estimates it has reached only about one-third of the growing pool of TTR prescribers. The company plans to increase customer-facing investment to broaden adoption, particularly among community-based physicians.
Alnylam estimated that approximately 200,000 U.S. ATTR-CM patients exist and that about 80% remain untreated. Management said investments in diagnosis and patient identification are intended to expand the treatable population and support earlier treatment.
Competition and TTR Development Outlook
Greenstreet said recent competitive developments reinforce Alnylam’s view of the TTR opportunity. The company noted a delay in expected U.S. generic entry for tafamidis until mid-2031 and cited the negative top-line result from the CARDIO-TTRansform study of eplontersen, which Alnylam expects could leave one fewer branded competitor in ATTR-CM.
Chief Research and Development Officer Pushkal Garg said the eplontersen study outcome has not changed Alnylam’s confidence in TRITON-CM, its Phase III cardiovascular outcomes study of investigational RNA interference therapy nucresiran. He said the company will review the full competitor data set when available and could consider changes involving patient enrollment or the trial’s analytic plan if warranted.
TRITON-CM is now expected to enroll roughly 1,750 patients and is designed as an event-driven trial. Garg said Alnylam believes nucresiran’s expected TTR knockdown profile differentiates it from eplontersen. Based on preliminary Phase I results, nucresiran produced more than 95% knockdown with twice-yearly dosing, according to the company.
Garg also cited results from the HELIOS-B and APOLLO-B studies as evidence supporting RNAi-mediated TTR silencing alongside stabilizer treatment. He said the company has observed treatment effects in patients using background stabilizers, while noting that Alnylam will continue assessing the detailed CARDIO-TTRansform data.
Pipeline and China Collaboration
Alnylam announced a collaboration with BeOne under which BeOne will receive exclusive commercialization and distribution rights for AMVUTTRA in mainland China and Macau, subject to marketing authorization. The companies plan to support awareness and diagnosis of ATTR amyloidosis in the regions.
The company also said it initiated a Phase II trial of ALN-6400 in von Willebrand disease and a Phase II trial of migalastat in Down syndrome-associated Alzheimer’s disease. In the second half of 2026, Alnylam expects four data readouts from three programs, including initial Phase I results for ALN-HTT02 in Huntington’s disease and Phase I data for ALN-2232 in obesity and weight management.
About Alnylam Pharmaceuticals (NASDAQ:ALNY)
Alnylam Pharmaceuticals, Inc (NASDAQ: ALNY) is a biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics. Founded to translate the scientific discovery of RNAi into new medicines, Alnylam applies small interfering RNA (siRNA) technology to silence disease-causing genes. The company develops therapies designed to provide durable disease modification by targeting underlying genetic drivers across a range of rare and more prevalent conditions.
Alnylam has advanced multiple siRNA-based products into commercialization, initially using lipid nanoparticle delivery and more recently employing GalNAc-conjugate chemistry to enable targeted delivery to the liver with subcutaneous dosing.
