FDA Accepts Alnylam’s sNDA for Vutrisiran for ATTR-CM

The US Food and Drug Administration (FDA) has accepted Alnylam Pharmaceuticals’ supplemental New Drug Application (sNDA) for vutrisiran for the treatment of transthyretin amyloidosis with cardiomyopathy (ATTR-CM).¹

Announced by Alnylam on November 25, 2024, the FDA set a Prescription Drug User Fee Act (PDUFA) target date of March 23, 2025, after the company filed a Priority Review voucher. As part of the sNDA acceptance, the FDA indicated no plan to hold an advisory committee meeting to review the investigational RNAi therapeutic.

“We are pleased that the FDA has accepted our sNDA for vutrisiran for the treatment of ATTR-CM – a steadily progressing, debilitating and ultimately fatal disease,” Pushkal Garg, MD, chief medical officer of Alnylam, said in a statement.¹

Vutrisiran has previously been FDA-approved for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN).² Vutrisiran delivers a rapid knockdown of mutant and wild-type TTR, confronting the underlying basis of ATTR.

This sNDA submission was based on full positive findings from the randomized, double-blind, placebo-controlled, multicenter, global Phase 3 HELIOS-B trial.¹ Results from HELIOS-B showed vutrisiran achieved statistical significance on the primary composite outcome of all-cause mortality and recurrent cardiovascular events.³

Upon analysis, vutrisiran achieved a 28% (hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.93; P = .01) relative risk reduction in the overall population, a 33% (HR, 0.67; 95% CI, 0.49 to 0.93; P = .016) relative risk reduction in the monotherapy population, and a 21% (HR, 0.79; 95% CI, 0.51 to 1.21) relative risk reduction in those with background tafamidis use.

Vutrisiran also demonstrated favorable effects on functional capacity (6-MWT: least-squares mean difference, 26.5 meters; 95% CI, 13.4 to 39.6; P <.001) and quality of life (KCCQ-OS score: least-squares mean difference, 5.8 points; 95% CI, 2.4 to 9.2; P <.001). Safety outcomes remained consistent with the established drug profile, with similar adverse event incidence between those receiving vutrisiran and placebo.

“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,” Garg added.¹

Pending FDA approval, Alnylam indicated vutrisiran could become the first therapeutic to manage the polyneuropathy manifestations of hATTR and cardiomyopathy manifestations of ATTR amyloidosis.

“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,” Garg said.¹

References

1. _{Alnylam announces U.S. Food and Drug Administration acceptance of Supplemental New Drug Application for vutris. Investor Relations | Alnylam Pharmaceuticals, Inc. November 25, 2024. Accessed November 26, 2024. https://investors.alnylam.com/press-release?id=28546.}
2. _{Alnylam announces FDA approval of AMVUTTRATM (Vutrisiran), an rnai therapeutic for the treatment of the polyn. Investor Relations | Alnylam Pharmaceuticals, Inc. June 13, 2024. Accessed November 26, 2024. https://investors.alnylam.com/press-release?id=26776.}
3. _{Campbell P. Vutrisiran reduces cardiovascular risk, improves quality of life in attr-cm. HCP Live. August 30, 2024. Accessed November 26, 2024. https://www.hcplive.com/view/vutrisiran-reduces-cardiovascular-risk-improves-quality-of-life-in-attr-cm.}