The U.S. Food and Drug Administration (FDA) has granted approval to BridgeBio Pharma's Attruby (acoramidis), an oral transthyretin (TTR) stabilizer, for the treatment of adult patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This approval marks a significant milestone in the treatment of ATTR-CM, offering a new therapeutic option aimed at reducing cardiovascular mortality and related hospitalizations.
Landmark Approval Based on Phase III Trial
The FDA's decision was primarily based on the results of the Phase III ATTRibute-CM trial, a randomized, double-blind, placebo-controlled study involving 632 patients with symptomatic ATTR-CM. Participants were randomized in a 2:1 ratio to receive either Attruby or a placebo over a 30-month period. The trial's primary endpoint was a composite measure including all-cause mortality, cardiovascular-related hospitalizations, levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and the six-minute walk test.
The ATTRibute-CM trial met its primary endpoint with a win ratio of 1.8, demonstrating a statistically significant benefit for patients treated with Attruby compared to placebo. Further evidence of Attruby's efficacy was observed in statistically significant improvements in the six-minute walk test and the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Notably, Attruby halved the increase in NT-proBNP levels compared to the placebo group, indicating a substantial impact on cardiac biomarkers.
Clinical Significance and Mechanism of Action
ATTR-CM is a progressive and often fatal disease characterized by the accumulation of misfolded TTR protein in the heart, leading to cardiac dysfunction. Attruby functions by stabilizing the TTR protein, preventing its misfolding and subsequent deposition in the heart tissue. This mechanism of action is particularly significant as Attruby is the first approved product with a label specifying near-complete TTR stabilization.
Future Plans and Global Expansion
BridgeBio is actively pursuing regulatory approvals for acoramidis in other regions, including Europe, Japan, and Brazil. A marketing authorization application (MAA) has been submitted to the European Medicines Agency (EMA), with a decision anticipated by 2025. Bayer has secured exclusive rights to commercialize acoramidis for ATTR-CM treatment in Europe, further expanding its potential reach.
In a gesture of gratitude, BridgeBio intends to provide Attruby free of charge for the lifetime of the U.S. trial participants. According to BridgeBio CEO Neil Kumar, the company's journey is not over as they look to pursue approvals globally and continue exploring the full potential of this treatment.
