FDA Accepts Alnylam's Supplemental NDA for Vutrisiran for ATTR Amyloidosis with Cardiomyopathy

CAMBRIDGE, Mass.--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leader in RNAi therapeutics, has announced that the U.S. Food and Drug Administration (FDA) has accepted for review the company’s supplemental New Drug Application (sNDA) for vutrisiran. This investigative RNAi therapeutic is being developed to treat ATTR amyloidosis with cardiomyopathy (ATTR-CM). Utilizing a Priority Review Voucher, the FDA has set a target action date of March 23, 2025, under the Prescription Drug User Fee Act (PDUFA). The FDA has also indicated that it does not plan to hold an advisory committee meeting to review this application.

Vutrisiran, known by its brand name AMVUTTRA®, is already approved by the FDA for treating the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. This therapeutic works by rapidly reducing levels of both mutant and wild-type transthyretin (TTR), targeting the root cause of transthyretin amyloidosis (ATTR). If vutrisiran gains approval for ATTR-CM, it would be the first treatment in the U.S. to address both the polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis.

Pushkal Garg, M.D., Chief Medical Officer of Alnylam, expressed satisfaction with the FDA’s acceptance of their sNDA for treating ATTR with cardiomyopathy, highlighting the debilitating and fatal nature of the disease. He noted that in the HELIOS-B study, vutrisiran improved cardiovascular outcomes, survival rates, disease progression, and quality of life compared to a placebo, even in patients receiving substantial background treatment. Garg looks forward to collaborating with the FDA to facilitate the review process and bring vutrisiran to patients with ATTR-CM in the U.S. by early next year.

The sNDA submission included positive results from the HELIOS-B study, a randomized, double-blind, placebo-controlled Phase 3 trial conducted globally with ATTR-CM patients. The study showed that vutrisiran had beneficial effects on mortality and cardiovascular events, as well as on functional capacity and quality of life in patients. These benefits were observed on top of substantial background standard care treatments. The safety and tolerability of vutrisiran were consistent with its established profile. Detailed findings from the study were presented at the European Society of Cardiology Congress and published in The New England Journal of Medicine on August 30, 2024.

AMVUTTRA® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of both mutant and wild-type transthyretin (TTR). It is administered quarterly via subcutaneous injection and is approved in over 15 countries for treating the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also being developed to treat ATTR amyloidosis with cardiomyopathy (ATTR-CM), which includes both wild-type and hereditary forms of the disease.

ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by the misfolding of transthyretin (TTR) proteins, leading to amyloid deposits in various body parts, such as nerves, heart, and gastrointestinal tract. Patients can present with polyneuropathy, cardiomyopathy, or both. The two forms of ATTR are hereditary ATTR (hATTR), due to a TTR gene variant affecting around 50,000 people globally, and wild-type ATTR (wtATTR), occurring without a TTR gene variant, affecting an estimated 200,000 – 300,000 people worldwide.

RNA interference (RNAi) is a natural cellular process of gene silencing, representing a significant and advancing frontier in biology and drug development. Discovered over a decade ago and recognized with the 2006 Nobel Prize for Physiology or Medicine, RNAi therapeutics harness this natural process to create a new class of medicines. Small interfering RNA (siRNA) molecules mediate RNAi by silencing messenger RNA (mRNA) before they encode disease-causing proteins, preventing their formation. This transformative approach has the potential to revolutionize treatment for genetic and other diseases.

Alnylam Pharmaceuticals, headquartered in Cambridge, MA, has pioneered RNAi therapeutics, translating this scientific breakthrough into innovative medicines. Its commercial products include ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) in partnership with Novartis. Alnylam continues to develop a robust pipeline of investigational medicines, aiming to deliver transformative treatments for both rare and common diseases globally.