Alnylam Pharmaceuticals (NASDAQ:ALNY) used a company webinar to highlight early commercial momentum for AMVUTTRA (vutrisiran) in ATTR cardiomyopathy (ATTR-CM), outline initiatives aimed at expanding diagnosis, and discuss how management views upcoming competitive and market-access dynamics in the category.
One year post-ATTR-CM approval, adoption and financial guidance in focus
Chief Commercial Officer Tolga Tanguler opened the event by marking one year since AMVUTTRA’s U.S. approval for ATTR-CM, calling it a “pivotal milestone” that expanded Alnylam beyond hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN) into a larger—though still orphan—cardiomyopathy population.
Operational metrics emphasized during the presentation included:
- More than 12,000 patients treated globally across the TTR franchise
- More than 1,600 unique U.S. prescribers since the ATTR-CM launch
- Approximately 90% of U.S. patients able to receive treatment within 10 miles of home
- Durable first-line access for about 90% of patients, with most paying $0 out of pocket
Alnylam also said AMVUTTRA reached an average of roughly 35% new-to-brand share across the first three quarters of the ATTR-CM launch as the “third entrant” in the market.
Market size estimates underscore diagnosis and treatment “headroom”
Senior Vice President and Head of U.S. business Mark Soued provided updated epidemiology estimates and framed category growth around three segments: untreated patients, new annual treatment starts, and patients progressing on stabilizers.
Soued said Alnylam now estimates nearly 200,000 ATTR-CM patients in the U.S., with more than 80% untreated, and approximately 500,000 patients globally. He also said the company estimates around 15,000 patients per year are new to treatment—up from roughly 10,000 estimated in October 2024. In addition, he cited observational data suggesting as many as half of patients on a common stabilizer progress, which he translated into roughly 15,000 patients today who may represent an opportunity for switching or add-on approaches.
Management argued diagnosis rates could rise materially over time, referencing benchmarks from diseases such as multiple sclerosis, pulmonary arterial hypertension, and atrial fibrillation. Soued said ATTR-CM diagnosis rates were about 2% prior to effective therapies, and suggested rates could eventually approach 70% as screening, guidelines, and treatment options evolve.
Clinical messaging centers on HELIOS-B outcomes and real-world dosing persistence
Dr. Sameer Bansilal, Vice President of Global Medical Affairs and a practicing cardiologist, focused on attributes he said cardiologists prioritize: mortality, cardiovascular hospitalizations, and quality of life. He said AMVUTTRA “rates very highly” on these attributes in cardiologist feedback presented during the webinar.
Discussing HELIOS-B, Bansilal said vutrisiran showed a “definitive and increasing benefit” on all-cause mortality to nearly 40% in the monotherapy population across the double-blind period and extended follow-up in the open-label extension. He also highlighted gastrointestinal symptoms as a common extracardiac burden in ATTR-CM, saying HELIOS-B showed patients treated with vutrisiran self-reported 40% fewer symptoms, with up to 65% lower incidence depending on the specific symptom.
Bansilal further pointed to serial cardiac MRI data from a subset of HELIOS-B patients at the U.K. National Amyloidosis Centre, describing reductions in amyloid burden and improvements in cardiac structure and function. He said amyloid regression was observed in 22% of patients in the vutrisiran group, compared with more than two-thirds progressing in the placebo arm, and characterized the improvement in left ventricular stroke volume as “quite striking,” while noting the MRI findings were in a small subset and are being studied further.
On treatment administration, Bansilal emphasized once-every-quarter healthcare professional dosing and said Alnylam has shown more than 90% persistence and adherence over more than a two-year period in real-world analyses in hATTR-PN. In Q&A, the company said it is seeing “very similar” adherence in ATTR-CM so far, while noting the older patient population and mortality can affect persistence metrics over time.
Competition, combination use, and tafamidis loss of exclusivity
Senior Vice President John Kennedy discussed competition within the TTR silencer class, pointing to Alnylam’s experience competing against eplontersen in hATTR-PN. He said that more than a year after competitor entry, Alnylam maintained about 70% share of new starts and more than 80% of total market share, while the overall category expanded.
Kennedy also addressed combination therapy dynamics, referencing AstraZeneca’s comments around expected combination data from CARDIO-TTRansform. He said HELIOS-B showed consistency of AMVUTTRA’s treatment effect with or without background tafamidis and that this is reflected in the label. He added the company is already seeing meaningful real-world combination use and expects additional real-world datasets to add evidence.
Separately, management discussed the anticipated loss of exclusivity (LOE) for tafamidis. Soued said Alnylam’s trajectory is not dependent on the timing of LOE, and argued the transition could be a tailwind by lowering the cost of dual-mechanism approaches. In Q&A, Soued said Pfizer has publicly stated it expects U.S. LOE for tafamidis in late 2028.
On payer dynamics, Alnylam repeatedly emphasized current access levels for AMVUTTRA, including about 99% coverage overall and about 90% confirmed first-line access, with most patients paying $0 out of pocket. Soued said Medicare fee-for-service represents roughly half of Alnylam’s ATTR-CM business and is covered to label with no step edits, which he said the company would expect to continue after tafamidis LOE.
New collaborations aimed at earlier diagnosis and coordinated care
Alnylam also highlighted investments and partnerships intended to increase earlier recognition and diagnosis of ATTR-CM. Kennedy described three stages in the diagnostic journey—awareness, suspicion, and diagnosis—and said tools such as nuclear scintigraphy exist, but earlier recognition remains the key opportunity.
Initiatives announced during the webinar included a collaboration with Viz.ai through the AWARE study. Kennedy said the project will develop ATTR-CM care pathways at five large U.S. integrated health systems, integrating an FDA-cleared Eko AI algorithm with electronic health records to help clinicians identify patients earlier and guide diagnostic evaluation and referral. He described AWARE as a prospective implementation study to evaluate AI-enabled screening in real-world workflows and generate evidence for broader adoption.
Kennedy also said Alnylam is working with the American Heart Association on a three-year initiative to strengthen systems of care for ATTR-CM through a national learning collaborative of multidisciplinary health systems focused on diagnosis, referral, treatment, and follow-up.
On global expansion, the company said AMVUTTRA has launched in Japan and Germany, and more recently in Austria and the U.K., with additional submissions and pricing and reimbursement negotiations ongoing. Management noted Germany’s rollout included a provisional launch during pricing negotiations and said the first quarter would reflect a negotiated cardiomyopathy price, with volume expected to offset early pricing-related headwinds given the higher prevalence of cardiomyopathy versus polyneuropathy.
Closing the webinar, Tanguler reiterated the company’s view that the U.S. could reach “upward of 75,000” treated ATTR-CM patients by 2030 and said Alnylam aims for AMVUTTRA to be the revenue leader in TTR by 2030, supported by physician preference, access and affordability, and a broad care network.
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.
