FDA Approves Alnylam’s Vutrisiran for the Treatment of ATTR Amyloidosis With Cardiomyopathy

This is a developing story and will be updated with new information as it becomes available.

The FDA has approved Alnylam Pharmaceuticals' subcutaneous RNA interface therapy vutrisiran, marketed as Amvuttra, for the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM).¹ The therapy is approved for adult patients.

The therapy is specifically meant to cut down on cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits. Vutrisiran was approved for ATTR-CM on the basis of a supplemental New Drug Application (sNDA) submitted by Alnylam; the therapy had previously been approved by the FDA on June 13, 2022, for polyneuropathy manifestations of hereditary ATTR Amyloidosis (hATTR-PN).^1,2

“The FDA approval of AMVUTTRA for ATTR-CM marks a pivotal advancement for patients, providing a new and clinically differentiated treatment option that has been shown to improve outcomes, including cardiovascular mortality, and reduce progression for those living with this devastating disease,” Yvonne Greenstreet, MBChB, the chief executive officer of Alnylam, said in a statement.¹ “I would like to extend my deepest gratitude to the patients who participated in our clinical trials, their families and caregivers, the clinical researchers, regulators, and my colleagues at Alnylam who made this approval possible. Today represents a significant milestone in our nearly 20 years of partnership with the ATTR amyloidosis community, but we are not stopping here. We will continue to innovate for patients with ATTR amyloidosis so they can live longer, better, healthier lives.”

The FDA's decision was based on data from the phase 3 HELIOS-B clinical trial (NCT04153149). Notably, the study attained statistically significant results compared to the placebo group for all prespecified end points, both primary and secondary, of which there were 10 in total. Vutisiran demonstrated the ability to effect a 28% decrease in the risk of all-cause mortality and recurrent cardiovascular events in the double-blind treatment period for the overall population, which lasted up to 36 months. Furthermore, through 42 months, mortality in this group was decreased by 36% in a prespecified secondary end point analysis that had 6 months of open-label extension on top of 36 months of the double-blind period. Functional capacity and quality of life were also shown to be preserved in patients treated with vutisiran in comparison to patients who received the placebo. Findings in HELIOS-B did not raise any new safety concerns regarding vutisiran, the safety profile of which was established in the phase 3 HELIOS-A study (NCT03759379) that enabled its previous approval in 2022 for hATTR-PN. Pain in extremity (15%), arthralgia (11%), dyspnea (7%), and decreased vitamin A (7%) constituted the most common adverse events related to vutisiran in HELIOS-A.

“This FDA approval provides an opportunity to further transform ATTR-CM treatment with a new mechanism of action," HELIOS-B investigator Ronald Witteles, MD, a professor of medicine at Stanford University School of Medicine and codirector of the Stanford Amyloid Center, added to the statement.¹ “The HELIOS-B clinical trial found that vutrisiran allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel. The trial enrolled patients who mirror the real-world population with this disease, and I am very encouraged by vutrisiran’s ability to demonstrate meaningful clinical benefits across both cardiovascular outcomes and multiple measures of disease progression. This is a very exciting day for patients with this challenging disease.”

Alnylam's sNDA for vutrisiran in ATTR-CM was accepted by the FDA in November 2024.³ The company utilized a Priority Review voucher. The agency did not deem an advisory committee meeting necessary prior to making its decision.

REFERENCES
1. Alnylam Announces FDA Approval of AMVUTTRA® (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular Death, Hospitalizations and Urgent Heart Failure Visits in Adults with ATTR Amyloidosis with Cardiomyopathy (ATTR-CM). News release. Alnylam Pharmaceuticals, Inc. March 20, 2025. Accessed March 20, 2025. https://investors.alnylam.com/press-release?id=28831
2. Alnylam announces FDA approval of Amvuttra (Vutrisiran), an RNAi therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. News release. Alnylam. June 13, 2022. Accessed June 14, 2022. https://investors.alnylam.com/press-release?id=26776
3. Alnylam Announces U.S. Food and Drug Administration Acceptance of Supplemental New Drug Application for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy. News release. Alnylam Pharmaceuticals, Inc. November 25, 2024. Accessed March 20, 2025. https://investors.alnylam.com/press-release?id=28546