The Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) for patisiran for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis.
The sNDA is supported by data from the phase 3, placebo-controlled APOLLO-B study (ClinicalTrials.gov Identifier: NCT03997383), which included 360 adult patients with ATTR amyloidosis (hereditary or wild-type) with cardiomyopathy. Results from the study showed that treatment with patisiran met the primary endpoint resulting in a statistically significant improvement from baseline in the 6-Minute Walk Test (6-MWT) at 12 months vs placebo (mean difference, 14.7 meters; P =.0162).
A statistically significant and clinically meaningful improvement in health-related quality of life (secondary endpoint; measured by the Kansas City Cardiomyopathy Questionnaire) was also observed in the patisiran arm when compared with placebo (P =.0397). With regard to the secondary composite endpoint of all-cause mortality, frequency of cardiovascular events, and change from baseline in 6-MWT over 12 months, a nonsignificant result (P =.0574) was found when patisiran was compared with placebo.
As for safety, infusion-related reactions, arthralgia, and muscle spasms were the most frequently reported adverse events. During the 12-month treatment period, no cardiac safety concerns relative to placebo were observed in patisiran-treated patients.
“ATTR amyloidosis with cardiomyopathy is an increasingly recognized cause of heart failure for which there are limited treatment options, said Rena N. Denoncourt, Vice President, TTR Franchise Lead, Alnylam. “The FDA’s acceptance of our sNDA for patisiran is a positive step forward as we work to bring patients with ATTR amyloidosis with cardiomyopathy a new treatment option that addresses the underlying cause of disease and has the potential to meaningfully improve functional capacity and quality of life.”
A Prescription Drug User Fee Act target date has been set for October 8, 2023. The FDA will be holding an advisory committee meeting to discuss the application.
Patisiran, a transthyretin-directed small interfering RNA, is currently approved under the brand name Onpattro for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
- Alnylam announces US Food and Drug Administration (FDA) acceptance of supplemental New Drug Application for Onpattro® (patisiran) for the treatment of the cardiomyopathy of ATTR amyloidosis. News release. Alnylam. February 21, 2023. https://www.businesswire.com/news/home/20230221005335/en/Alnylam-Announces-U.S.-Food-and-Drug-Administration-FDA-Acceptance-of-Supplemental-New-Drug-Application-for-ONPATTRO%C2%AE-patisiran-for-the-Treatment-of-the-Cardiomyopathy-of-ATTR-Amyloidosis.
- Alnylam presents positive results from the APOLLO-B phase 3 study of patisiran in patients with ATTR amyloidosis with cardiomyopathy. News release. Alnylam. September 8, 2022. https://investors.alnylam.com/press-release?id=26936.