FDA Approves Vutrisiran to Mitigate Cardiomyopathy-Related Risks and Conditions

The FDA has approved vutrisiran (Amvuttra; Alnylam Pharmaceuticals) for adult patients with cardiomyopathy classified as either hereditary transthyretin-mediated amyloidosis (ATTR-CM) or wild-type. With this announcement, vutrisiran becomes the only approved RNA interference (RNAi) intervention to mitigate cardiovascular-related hospitalizations and deaths, as well as urgent visitations for heart failure.¹

Currently there is no cure for cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis. | image credit: Tom - stock.adobe.com

“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, chief executive officer, Alnylam, commented in a statement.

Throughout the US, ATTR-CM impacts an estimated 150,000 individuals. This condition progresses quickly, with no known cure, and often becomes fatal. One of the pertinent challenges today for those affected is that they are often undiagnosed—and therefore are not treated. For those aware of their condition and who undergo treatment, disease progression still remains likely.

This RNAi therapy works to counteract transthyretin (TTR) fibrils. As TTR is deposited, it causes permanent cardiovascular damage that ultimately leads to premature mortality. Vutrisiran is administered subcutaneously 4 times per year and aims to disrupt the production of TTR directly, greatly impacting the buildup of TTR fibrils.

“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,” Muriel Finkel, president, Amyloidosis Support Groups, said in a statement. “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.”

The FDA approval was informed by the HELIOS-B trial (NCT04153149), which found that patients’ all-cause mortality and the recurrence of cardiovascular episodes were reduced by 28% over a 36-month study period.² After the 2-month mark, researchers observed a 36% reduction in patient mortality. These results came from the double-blind period comparing vutrisiran with placebo; however, the monotherapy portion of the study also suggested that patients were 33% less likely to experience a cardiovascular episode and 35% less likely to experience mortality after 42 months.

For the great majority of patients, vutrisiran requires $0 out-of-pocket, and is covered by approximately 99% of patients’ insurance.¹

Among the adverse events reported, the most prevalent were reduced vitamin A levels (7%), dyspnea (7%), arthralgia (11%), and pain (15%).

“[This] represents a significant milestone in our nearly twenty 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,” stated Greenstreet.

Additionally, this FDA decision marks vutrisiran as the sole intervention indicated for both ATTR-CM and polyneuropathy of hereditary transthyretin-mediated amyloidosis in adult populations.

Vutrisiran was already approved to treat polyneuropathy manifestations of ATTR amyloidosis.³

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). Business Wire. 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. 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

3. Meglio M. FDA approves vutrisiran to treat hATTR amyloidosis. NeurologyLive^®. June 14, 2022. Accessed March 21, 2025. https://www.neurologylive.com/view/fda-approves-vutrisiran-to-treat-hattr-amyloidosis