FDA Accepts sNDA ATTR Amyloidosis Drug, Vutrisiran

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The FDA has accepted a supplemental new drug application for Alnyam’s vutrisiran, an investigational drug being developed for the treatment of transthyretin amyloidosis with cardiomyopathy (ATTR-CM). A Prescription Drug User Fee Act (PDUFA) date has been set for March 23, 2025, according to a news release published yesterday.

ATTR-CM is a rare, rapidly progressing and fatal disease in which misfolded transthyretin (TTR) proteins amyloid deposits collect in places such as the nerves, heart and gastrointestinal tract. There are two types of ATTR - hereditary ATTR which affects about 50,000 people worldwide and wild-type ATTR, which affects between 200,000 and 300,000 people across the globe. Vutrisiran works by silencing both mutant and wild-type transthyretin through RNA interference, thus eliminating mutations.

Vutrisiran is the generic name for Amvuttra, which is currently FDA-approved to treat adults with the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN). If approved, vutrisiran would become the first therapy in the United States to treat both the polyneuropathy manifestations of hATTR and cardiomyopathy manifestations of ATTR amyloidosis, the news release said.

Amvuttra is a subcutaneous drug administered every three months in the abdomen, thighs or upper arms. The recommended dose is 25 mg/0.5 mL. Amvuttra has a wholesale acquisition cost of $119,351 per prefilled syringe.

The SNDA acceptance of vutrisiran was based on the successful results of the HELIOS-B trial in which vutrisiran reduced the risk of all-cause mortality and recent cardiovascular events by 28%, when compared with placebo, study results show. In the overall population, treatment with vutrisiran resulted in less of a decline in distance on the six-minute walk test. Results from the HELIOS-B study were also published in The New England Journal of Medicine.

The safety and tolerability of vutrisiran were consistent with Amvuttra results and the most common side effects were extremity pain (15%), arthralgia (11%) dyspnea (7%) and vitamin A deficiency (7%), which can be treated with a vitamin A supplement.

“These HELIOS-B data also suggest that, within this current patient population, vutrisiran may provide greater benefit to patients in earlier stages of the disease where, due to the progressive nature of ATTR-CM, early treatment can more effectively preserve functional capacity and quality of life,” Marianna Fontana, M.D., Ph.D., HELIOS-B investigator and cardiology professor at the University College London, said in a news release.

Financial assistance programs are available for Amvuttra patients through Alnyam Assist. The Alnylam Assist Commercial Copay Program covers certain out-of-pocket costs for eligible patients who have commercial coverage and the Alnylam Assist Patient Assistance Program provides Amvuttra at no-cost to uninsured patients who meet certain criteria.