− Reductions in All-Cause Mortality and Recurrent Cardiovascular Events Maintained Across Key Patient Subgroups, Including Patients Taking a Broad Range of Heart Failure Therapies –
− Pooled Analysis of Over 25,000 Patient-Years of Experience with TTR-Silencing RNAi Therapies Shows a Consistent Safety Profile, Including No Clinically Meaningful Ocular Effects of Vitamin A Lowering –
− DemonsTTRate Study Designed to Generate Long-Term Real-World Evidence in More Than 2,000 Patients with ATTR-CM −
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced new analyses from the HELIOS-B Phase 3 study of vutrisiran in patients with the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM), adding to the growing body of evidence supporting vutrisiran and reinforcing the durability of transthyretin (TTR) knockdown and its well-characterized safety profile. Vutrisiran is the first and only TTR silencer approved for ATTR-CM that is designed to deliver rapid knockdown of TTR at the source. The data presented at Heart Failure 2026, the annual congress of the Heart Failure Association of the European Society of Cardiology, show consistent clinical benefit across patient populations commonly encountered in clinical practice, including those with a high disease burden, supporting its use as a first-line treatment option for this rapidly progressive and life-threatening disease.
“The analyses presented at Heart Failure 2026 provide important insights into how vutrisiran performs across the patients we see in clinical practice, including those who present with features such as atrial fibrillation, low systolic blood pressure and a high comorbidity burden,” said Scott Solomon, M.D., Professor of Medicine at Harvard Medical School and cardiologist at Brigham and Women’s Hospital. “These new HELIOS-B analyses show that the clinical benefits of vutrisiran were maintained across these clinically complex patient groups, as well as in patients receiving background therapies, including TTR stabilizers and disease-modifying heart failure therapies, reinforcing both the consistency of the treatment effect and its relevance in real-world clinical practice. Taken together, these findings support the use of vutrisiran as a first-line treatment option for ATTR-CM across a broad range of patient populations.”
In patients with atrial fibrillation, representing approximately 65% of the HELIOS-B study population and associated with more advanced disease, vutrisiran significantly reduced the risk of all-cause mortality and recurrent cardiovascular (CV) events compared with placebo. Treatment effects were also maintained in patients with low systolic blood pressure (SBP), a higher-risk phenotype, with vutrisiran slowing the progressive decline in SBP observed over time. Clinical benefits were similarly consistent regardless of comorbidity burden or concomitant use of disease-modifying therapies, including tafamidis and heart failure medications such as SGLT2 inhibitors, MRAs, ß-blockers and ACEi/ARB/ARNI. Consistent effects were also observed in women, a historically underrepresented population in ATTR-CM trials.
A separate pooled analysis of clinical trial and post-marketing safety data evaluated the relationship between transthyretin-lowering RNAi therapies and vitamin A deficiency-related adverse events. Patients treated with vutrisiran and patisiran are suggested to take the recommended daily allowance of vitamin A. The analysis included more than 25,000 patient-years of treatment exposure across vutrisiran and patisiran programs. Rates of ocular adverse events potentially associated with vitamin A deficiency were low and comparable to placebo. No cases of clinically meaningful vitamin A deficiency were observed.
“Vitamin A plays an essential role in vision and other key physiological functions. While transthyretin contributes to its transport, multiple pathways support its delivery throughout the body,” said William S. Blaner, Ph.D., Professor of Nutritional Medicine at Columbia University and expert in vitamin A metabolism and transport. “The low and comparable to placebo rates of vitamin A deficiency-related adverse events observed in this large analysis provide strong reassurance that lowering transthyretin does not meaningfully increase these events in patients with ATTR amyloidosis.”
Alnylam also presented the design and rationale of the DemonsTTRate study, a global, prospective, observational study evaluating real-world outcomes in patients with ATTR-CM. The study is expected to enroll more than 2,000 patients and follow them for up to five years, generating longitudinal data on clinical outcomes, treatment patterns and healthcare utilization across routine clinical practice.
Across ATTR-CM and hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN), worldwide experience with vutrisiran to date exceeds 13,000 patient-years, reflecting a robust and expanding body of clinical evidence across both manifestations of the disease. To view Alnylam’s Heart Failure 2026 presentations please visit Capella.
AMVUTTRA® (vutrisiran) INDICATIONS AND IMPORTANT SAFETY INFORMATION
Indications
In the EU, AMVUTTRA® (vutrisiran) is indicated for the treatment of:
- hereditary transthyretin amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy (hATTR-PN).
- wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM).
Availability across the EU is subject to local reimbursement timelines.
Important Safety Information
Reduced Serum Vitamin A Levels and Recommended Supplementation
Vutrisiran treatment leads to a decrease in serum vitamin A levels. Supplementation of approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day is advised for patients taking vutrisiran. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).
Adverse Reactions
Commonly reported adverse reactions with vutrisiran were injection site reactions and increase in blood alkaline phosphatase and alanine transaminase.
For additional information about vutrisiran, please see the full Summary of Product Characteristics.
About AMVUTTRA® (vutrisiran)
AMVUTTRA® (vutrisiran) is a transthyretin (TTR) silencer that delivers rapid knockdown of TTR at the source to address the underlying cause of transthyretin amyloidosis (ATTR). In a clinical study, AMVUTTRA rapidly knocked down TTR in as early as six weeks and decreased TTR levels by 87% with two and a half years of treatment. It is approved as a treatment for the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults and for the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults in various countries, globally. Administered quarterly via subcutaneous injection, AMVUTTRA is the first and only silencer approved for the treatment of ATTR-CM and hATTR-PN.
About Transthyretin Amyloidosis (ATTR)
Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by pathogenic transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart, and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant. It is estimated that more than 500,000 people worldwide live with ATTR.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is a leading global biopharmaceutical company and the pioneer of the RNA interference (RNAi) revolution. The Company is focused on developing transformative therapies with the potential to prevent, halt, or reverse disease. For more than two decades, Alnylam has advanced the Nobel-Prize-winning science of RNAi, delivering critical breakthroughs and six approved medicines. Alnylam has medicines available in more than 70 countries and a rapidly expanding and robust pipeline, in addition to consistently being recognized as an exceptional workplace and socially responsible organization. The Company is executing on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health.
Alnylam Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects, including, without limitation, statements regarding the potential for vutrisiran to be used as a first-line treatment for ATTR-CM; the potential efficacy of vutrisiran in patients who present with features such as atrial fibrillation, low systolic blood pressure and a high comorbidity burden; the number of patients who will be enrolled in the DemonsTTRate study, the duration of the follow-up period for those patients, and the data the study will generate; and Alnylam’s ability to execute on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “Alnylam 2030” strategy; Alnylam’s ability to successfully launch, market and sell Alnylam’s approved products globally, including AMVUTTRA; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; delays, interruptions or failures in the manufacture and supply of Alnylam’s marketed products or its product candidates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation and government investigations; the risk of future litigation and government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s 2025 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.
Contacts
Alnylam Pharmaceuticals, Inc.
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(Investors and Media)
+1-617-682-4340
Josh Brodsky
(Investors)
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