FDA Panel Votes in Favor of Patisiran for Cardiomyopathy of ATTR Amyloidosis

The Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee voted in favor (9 “yes” to 3 “no”) that the benefits of patisiran outweigh its risks for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis.

The panel’s recommendation was based on efficacy and safety data that included results 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. Study participants were randomly assigned to receive patisiran 0.3mg/kg or placebo intravenously every 3 weeks for 12 months.

Findings 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. Moreover, the patisiran arm achieved a statistically significant and clinically meaningful improvement in health-related quality of life (measured by the Kansas City Cardiomyopathy Questionnaire [KCCQ-OSS]) compared with the placebo arm. 

While the panel supported the approval of patisiran, they expressed concerns over the design of the APOLLO-B trial. Specifically, they noted that the effects of patisiran were small and of questionable clinical meaningfulness, and were confined to patients not on background therapy with tafamidis. Moreover, the panel recommended the use of anchor-based methods to aid in the clinical meaningfulness of 6MWT or KCCQ-OSS.

Although not bound to the committee’s recommendations, the FDA does take them into consideration when making decisions on approval. A regulatory decision is expected by October 8, 2023.

Pushkal Garg, MD, Chief Medical Officer at Alnylam, commented: “The positive outcome of today’s meeting is supported by the efficacy and safety data observed in the APOLLO-B Phase 3 study, and is another step toward bringing patients with the cardiomyopathy of ATTR amyloidosis a novel treatment option that addresses the underlying cause of disease and has the potential to meaningfully benefit patients’ functional capacity and quality of life. We look forward to continuing to work with the FDA as they complete their review of our sNDA.”

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.

This article originally appeared on MPR