FDA Approves Vutrisiran (AMVUTTRA) for ATTR-CM
The approval expands the indication for vutrisiran, which becomes the first therapeutic approved by the FDA for the treatment of ATTR-CM.
Credit: US Food and Drug Administration
The US Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for vutrisiran (AMVUTTRA) for the treatment of adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM).1
Announced by Alnylam, on March 20, 2025, with this expanded indication, vutrisiran becomes the first approved RNAi therapeutic targeted to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits in ATTR-CM.
“This FDA approval provides an opportunity to further transform ATTR-CM treatment with a new mechanism of action. The HELIOS-B clinical trial found that vutrisiran allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel,” said Ronald Witteles, MD, a professor of medicine at Stanford University School of Medicine, co-director of the Stanford Amyloid Center, and HELIOS-B investigator.1 “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.”
A rapidly progressive, fatal disease, ATTR-CM is estimated to impact nearly 150,000 individuals in the US and more than 300,000 worldwide. Without a cure, the deposition of misfolded TTR fibrils can lead to irreversible damage and premature death. As most patients remain undiagnosed, a notable number of those treated with commonly used therapies experience disease progression.2
“The FDA approval of [vutrisiran] 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,” said Yvonne Greenstreet, MBChB, chief executive officer of Alnylam.1
Vutrisiran, an RNAI therapeutic, provides a rapid knockdown of TTR with 4 subcutaneous doses per year—with this rapid knockdown of TTR production, the therapy can notably lower the deposition of TTR fibrils.1
Approval was awarded based on the Phase 3 HELIOS-B clinical trial, with vutrisiran achieving statistical significance on cardiovascular benefit in ATTR-CM versus placebo on all 10 pre-specified primary and secondary endpoints. Conducted across 87 sites in 26 countries, the double-blind, placebo-controlled trial randomized 655 patients to receive vutrisiran 25 mg or placebo subcutaneously every three months for up to 36 months.3
Vutrisiran achieved all primary and secondary endpoints. The treatment was associated with a 28% reduction in risk for all-cause mortality and recurrent cardiovascular events in the overall population (HR, 0.72; 95% CI, 0.56-0.93; P = .01) and a 33% reduction among those receiving monotherapy (HR, 0.67; 95% CI, 0.49-0.93; P = .016). Among individuals on background tafamidis, the risk reduction was 21% (HR, 0.79; 95% CI, 0.51-1.21).
Further analysis of secondary outcomes also favored vutrisiran, with a reduction in all-cause mortality over 42 months in the overall (HR, 0.64; 95% CI, 0.46-0.90; P = .01) and monotherapy groups (HR, 0.65; 95% CI, 0.44-0.97; P = .045). Patients receiving vutrisiran also showed improvements in 6-minute walk test distance (mean difference, 26.5 meters; P < .001) and Kansas City Cardiomyopathy Questionnaire Overall Summary score (mean difference, 5.8 points; P < .001).
Safety analysis revealed similar adverse event rates between groups, with serious adverse events occurring in 62% of vutrisiran-treated patients and 67% of placebo-treated patients. Alnylam indicated no new safety concerns were identified in the HELIOS-B clinical trial among patients with ATTR-CM.
The FDA previously approved the therapy for adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in June 2022, based on positive results from the HELIOS-A clinical trial.4
“Despite recent advances, there remains a significant need for patients living with ATTR-CM and I’ve witnessed, firsthand, the impact that ATTR amyloidosis can have on families, including diminished quality of life and the loss of loved ones,” said Muriel Finkel, president of the Amyloidosis Support Groups.1 “The availability of this groundbreaking treatment option is a significant moment for patients living with ATTR amyloidosis. It represents a beacon of hope for our community.”
References
Alnylam announces FDA approval of AMVUTTRA® (vutrisiran), the first rnai therapeutic to reduce cardiovascular. Investor Relations | Alnylam Pharmaceuticals, Inc. March 20, 2025. Accessed March 20, 2025. https://investors.alnylam.com/press-release?id=28831.
Jain A, Zahra F. Transthyretin Amyloid Cardiomyopathy (ATTR-CM) [Updated 2023 Apr 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574531/
Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med. 2025;392(1):33-44. doi:10.1056/NEJMoa2409134
Grossi G. FDA approves rnai therapeutic vutrisiran for Hattr Amyloidosis. HCP Live. June 14, 2022. Accessed March 20, 2025. https://www.hcplive.com/view/fda-approves-rnai-therapeutic-vutrisiran-for-hattr-amyloidosis.
