Alnylam Submits sNDA for Vutrisiran for Treatment of ATTR-CM

Alnylam Pharmaceuticals, Inc. has announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM).¹

Announced by Alnylam, on October 9, 2024, the sNDA submission was based on the full positive findings from the Phase 3 HELIOS-B trial. As part of the sNDA submission, the company has indicated it will utilize a Priority Review voucher to accelerate the FDA review timeline.

“We are proud that with this first regulatory submission, we are a significant step closer to bringing vutrisiran to patients with ATTR amyloidosis with cardiomyopathy, which is a steadily progressive, debilitating, and ultimately fatal disease,” said Pushkal Garg, MD, chief medical officer, Alnylam.¹

ATTR is a rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins accumulating as amyloid deposits in the body, including in the nerves, heart, and gastrointestinal tract.² An underdiagnosed condition, there are two forms of ATTR: hereditary ATTR (hATTR) caused by a TTR gene variant and wild-type ATTR (wATTR) which occurs without a TTR gene variant.

Vutrisiran is an RNAi therapeutic delivering rapid knockdown of both hATTR and aWTTR in development for the treatment of ATTR-CM. Vutrisiran (AMVUTTRA®) is currently FDA-approved for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.³

The sNDA application was based on positive findings from HELIOS-B, a Phase 3 randomized, double-blind, placebo-controlled, multi-center global study designed to evaluate the efficacy and safety of vutrisiran in ATTR-CM.¹ The reduction of all-cause mortality and recurrent cardiovascular events served as the primary composite endpoint in patients with ATTR-CM.

A total of 655 adult patients with ATTR-CM were randomized 1:1 to vutrisiran 25mg or placebo subcutaneously once every three months during a double-blind treatment period of up to 36 months. After a double-blind period, all eligible patients could receive vutrisiran in an open-label extension period of HELIOS-B.

Upon analysis, HELIOS-B showed the favorable effect of vutrisiran on mortality and cardiovascular events, functional capacity, and quality of life in patients with ATTR-CM. Safety was consistent with the established profile of vutrisiran. Overall, the rates of adverse events (AEs), serious AEs, severe AEs, and AEs leading to study drug discontinuation remained similar between the vutrisiran and placebo arms.

“HELIOS-B demonstrated rapid knockdown of TTR with vutrisiran and an improvement in death and cardiovascular events, as well as delays in disease progression, with vutrisiran as compared to placebo, with consistent effects across all pre-specified subgroups,” Garg added.¹

In their announcement, Alnylam indicated that vutrisiran could represent a first-line treatment option for ATTR-CM, and it looks forward to continuing working with the FDA on the sNDA to ensure the medication’s approval.

“We believe that, pending regulatory approval, vutrisiran has the potential to become a first-line therapy for ATTR-CM,” Garg said.¹ “We look forward to working with the FDA over the coming months on this application to bring this medicine to patients as rapidly as possible.”

References

1. _{Alnylam submits Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration for Vutrisir. Investor Relations | Alnylam Pharmaceuticals, Inc. October 9, 2024. Accessed October 11, 2024. https://investors.alnylam.com/press-release?id=28446.}
2. _{Galant NJ, Westermark P, Higaki JN, Chakrabartty A. Transthyretin amyloidosis: an under-recognized neuropathy and cardiomyopathy. Clin Sci (Lond). 2017;131(5):395-409. doi:10.1042/CS20160413}
3. _{Alnylam announces FDA approval of AMVUTTRATM (Vutrisiran), an rnai therapeutic for the treatment of the polyn. Investor Relations | Alnylam Pharmaceuticals, Inc. June 13, 2022. Accessed October 11, 2024. https://investors.alnylam.com/press-release?id=26776.}