FDA Accepts Alnylam’s Application for Cardiomyopathy Treatment

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Alnylam Pharmaceuticals announced on Nov. 25, 2024 that FDA has accepted the company’s supplemental new drug application (sNDA) for the RNAi drug, vutrisiran, for the treatment of transthyretin amyloidosis with cardiomyopathy (ATTR-CM). An action date of March 23, 2025 has been set by FDA under the Prescription Drug User Fee Act due to a Priority Review Voucher. Vutrisiran is a generic version of the FDA-approved branded drug AMVUTTRA, used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.

Vutrisiran treats the cause of ATTR by “knocking down” mutant and wild-type transthyretin. Should the drug be approved by FDA, it will be the first one to treat both the polyneuropathy manifestations of hATTR and cardiomyopathy manifestations of ATTR amyloidosis in the United States.

The sNDA was based on results from the randomized, double-blind, placebo-controlled multicenter global Phase III study, HELIOS-B, which showed favorable effects on “outcomes of death and cardiovascular events, functional capacity, and quality of life in patients with ATTR-CM. These treatment effects were seen on top of substantial background standard of care treatments. Vutrisiran demonstrated encouraging safety and tolerability consistent with the established profile of the drug,” (1).

Adverse reactions to vutrisiran include pain in extremities, arthralgia, dyspnea, and a decrease in vitamin A. The company stated in the press release that, because of the vitamin A reduction, “supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.”

“We are pleased that the FDA has accepted our sNDA for vutrisiran for the treatment of ATTR with cardiomyopathy—a steadily progressing, debilitating, and ultimately fatal disease,” said Pushkal Garg, MD, chief medical officer of Alnylam, in a press release (1). “In HELIOS-B, treatment with vutrisiran improved cardiovascular outcomes, survival, disease progression, and quality of life, as compared to placebo, in a population reflective of today’s patients on substantial background treatment. We look forward to working with the FDA to support their review of the application and bring vutrisiran to patients with ATTR-CM in the US early next year.”

FDA approved another ATTR-CM drug on Nov. 22, 2024. BridgeBio Pharma’s Attruby (acoramidis) was approved for the treatment of adults with ATTR-CM to reduce cardiovascular death and cardiovascular-related hospitalization (2). Results from the ATTRibute-CM Phase III study showed the drug reduced death and cardiovascular-related hospitalization, according to BridgeBio.

“We are excited to be part of the celebration for the FDA approval of Attruby. The need for more treatment options for patients living with ATTR-CM is crucial to achieving the goal of better outcomes and improved quality of life. Access to this new therapy means more hope and more opportunity to improve the lives of patients with amyloidosis,” said Muriel Finkel, president of Amyloidosis Support Groups, a non-profit organization dedicated to the support of amyloidosis patients and caregivers, in the press release (2).

"Transthyretin cardiac amyloidosis is a progressive disease with a poor prognosis when left untreated. Having a new first line treatment option which provides excellent TTR stabilization and improves outcomes in this disease gives patients more options,” said Martha Grogan, MD, of the Mayo Clinic, in the release. “Encouraging data suggests Attruby reduces all-cause mortality and cardiovascular hospitalization as early as three months after initiation of therapy. With continued advances in therapy, this previously fatal disease is becoming a manageable chronic cardiovascular condition."

References

1. Alnylam. Alnylam Announces U.S. Food and Drug Administration Acceptance of Supplemental New Drug Application for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy. Press Release. Nov. 25, 2024.
2. BridgeBio Pharma. Attruby™ (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients. Press Release. Nov. 22, 2024.