Alnylam Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) for vutrisiran, an investigational RNAi therapeutic, for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of March 23, 2025.
The sNDA is based on positive results from the HELIOS-B Phase 3 study, a randomized, double-blind, placebo-controlled, multicenter global trial in patients with ATTR-CM. The FDA has indicated that it does not plan to hold an advisory committee meeting to review the application.
Vutrisiran, known commercially as AMVUTTRA for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN), works by rapidly knocking down both mutant and wild-type transthyretin (TTR), addressing the underlying cause of ATTR. If approved, vutrisiran would be the first therapeutic approved in the U.S. to treat both the polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis.
Clinical Efficacy in HELIOS-B
The HELIOS-B study demonstrated that vutrisiran had favorable effects on death and cardiovascular events, functional capacity, and quality of life in patients with ATTR-CM. These treatment effects were observed on top of substantial background standard of care treatments. The safety and tolerability profile of vutrisiran in the study was consistent with its established profile.
Detailed results from the HELIOS-B study were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine on August 30, 2024.
Vutrisiran: Mechanism of Action
Vutrisiran is an RNAi therapeutic designed to inhibit the production of transthyretin (TTR) protein, which, when misfolded, leads to amyloid deposits in various tissues and organs, causing ATTR. By reducing the amount of TTR protein, vutrisiran aims to slow or halt the progression of the disease.
About ATTR Amyloidosis
Transthyretin amyloidosis (ATTR) is a progressive and fatal disease caused by misfolded transthyretin (TTR) proteins that accumulate as amyloid deposits in the nerves, heart, and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy, or both. Hereditary ATTR (hATTR) is caused by a TTR gene variant and affects approximately 50,000 people worldwide, while wild-type ATTR (wtATTR) occurs without a TTR gene variant and impacts an estimated 200,000 – 300,000 people worldwide.
Alnylam's Perspective
"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, M.D., Chief Medical Officer of Alnylam. "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 U.S. early next year."
