FDA Decides Not to Approve Patisiran in ATTR Cardiomyopathy

The US Food and Drug Administration on Monday declined to approve an expanded indication for patisiran (Onpattro, Alnylam Pharmaceuticals) for the treatment of transthyretin-amyloid cardiomyopathy (ATTR-CM).

The FDA’s decision came after positive 12-month results from the APOLLO-B phase III study and 24-month and 18-month data from an open-label-extension trial. In the main study, patisiran met the primary endpoint of a statistically significant improvement in 6-minute walk test compared to placebo at 12 months as well as the first secondary endpoint of a statistically significant improvement in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ).

The FDA rejection comes as a surprise because the agency’s own Cardiovascular and Renal Drugs Advisory Committee seemingly threw their support behind the expanded indication. Last month, the committee voted 9 to 3 that the benefits of patisiran outweigh its risks for the treatment of ATTR-CM. While FDA isn’t required to follow guidance from their advisory committees, they frequently do.

The FDA’s decision yesterday also caught some HF experts off guard. In a thread on X, Ronald Witteles, MD (Stanford University School of Medicine, CA), who heads up the Stanford Amyloid Center, called the FDA’s decision “a major miss.”

Patisiran is currently indicated for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults, but the FDA’s move this week, conveyed in a Complete Response Letter to Alnylam, means the company will now stop pursuing the expanded indication in the US.