FDA Approves Vutrisiran to Reduce Cardiovascular Death, Hospitalizations in Patients With ATTR-CM

Vutrisiran becomes the first and only therapeutic FDA-approved to treat cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults.

Updated on Friday, March 21, 2025, at 11:13 AM.

The FDA approved vutrisiran (Amvuttra; Alnylam Pharmaceuticals) for the treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits.¹ The approval is supported by results from the phase 3 HELIOS-B clinical trial (NCT04153149)², which were published in The New England Journal of Medicine and presented at the European Society of Cardiology Congress.³

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ATTR-CM is a rapidly progressive—and ultimately fatal—disease estimated to affect about 150,000 people in the US and over 300,000 people worldwide. There is currently no cure for ATTR-CM, and the deposition of misfolded transthyretin (TTR) fibrils causes irreversible damage over time, eventually leading to premature death. Most patients remain undiagnosed and untreated, and a significant portion of those who are treated with commonly used therapies experience disease progression.¹

Vutrisiran is an RNAi therapeutic that works upstream to deliver rapid knockdown of TTR, addressing the disease at its source. By rapidly knocking down TTR production, it substantially decreases the deposition of TTR fibrils, which form amyloid, causing irreversible cardiovascular damage and premature death in patients with ATTR-CM. It only requires 4 subcutaneous doses per year, meaning it can be convenient for patients.¹

“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,” Yvonne Greenstreet, MBChB, CEO of Alnylam Pharmaceuticals, said in a news release. “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.”¹

HELIOS-B (NCT04153149) was a randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial that evaluated the efficacy and safety of vutrisiran in patients with ATTR-CM amyloidosis. A total of 655 patients were enrolled and randomly assigned to receive either 25 mg of vutrisiran subcutaneously (n = 326) or placebo (n = 329) once every 3 months for up to 36 months.^2,3

The primary end point was a composite death from and cause of recurrent cardiovascular events. Secondary end points included death from any cause as well as changes from baseline in the distance covered on the 6-minute walk test and Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score. Additionally, efficacy end points were assessed in the overall population and in the monotherapy population (the patients who were not receiving tafamidis at baseline) and were tested hierarchically.^2,3

The study results indicated that treatment led to a lower risk of death from any cause and recurrent cardiovascular events compared with placebo (overall population HR: 0.72 [95% CI, 0.56-0.93]; P = .01; monotherapy population HR: 0.67 [95% CI, 0.49-0.93]; P = .02), as well as a lower risk of death from any cause through a 42-month duration (overall population HR: 0.65 [95% CI, 0.46-0.90]; P = .01). Among the patients in the overall population, 125 and 159 patients in the vutrisiran and placebo groups, respectively, had at least 1 primary end point event.³

Further, in the overall population, treatment with vutrisiran resulted in less of a decline in the distance covered on the 6-minute walk test than placebo (least-squares mean difference: 26.5 m [95% CI, 13.4-39.6]; P < .001) and less of a decline in the KCCQ-OS score (least-squares mean difference: 5.8 points [95% CI, 2.4-9.2]; P < .001). Similar benefits were also observed in the monotherapy population.

“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,” study investigator Ronald Witteles, MD, professor of medicine at Stanford University School of Medicine and codirector of the Stanford Amyloid Center, said in the news release. “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.”¹

About the Trial

Trial Name: HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy.

ClinicalTrials.gov ID: NCT04153149

Sponsor: Alnylam Pharmaceuticals

Completion Date (Estimated): December 1, 2026

The incidence of adverse events (AEs) was shown to be similar in the 2 groups (99% in the vutrisiran group, 98% in the placebo group), with serious AEs occurring in approximately 62% and 67% of patients in the vutrisiran and placebo groups, respectively. No new safety concerns were identified in this study.³ In another study featuring patients with hATTR-PN, the most common AEs in those treated with vutrisiran were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and decreases in vitamin A (7%).¹

“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,” Muriel Finkel, president of the Amyloidosis Support Groups, said in the news release. “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.”¹

REFERENCES

1. Businesswire. 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. March 20, 2025. Accessed March 21, 2025. https://www.businesswire.com/news/home/20250319752041/en/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

2. HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy. ClincialTrials.gov identifier: NCT04153149. Updated February 17, 2025. Accessed March 21, 2025. https://clinicaltrials.gov/study/NCT04153149

3. 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