Acoramidis is an oral small molecule to treat patients with transthyretin amyloid cardiomyopathy.
BridgeBio Pharma has submitted a new drug application to the FDA for acoramidis to treat patients with transthyretin amyloid cardiomyopathy (ATTR-CM), a type of heart failure in older adults. ATTR-CM is a rare disease that leads to a build-up of the protein transthyretin in the left ventricle of the heart, leading to a thickening of the heart muscle.
Acoramidis is an oral small molecule stabilizer of transthyretin. It was designed to mimic the protective effects of T119M mutation, which has been associated with reduced risk of vascular events.
The application was based on positive results from the phase 3 ATTRibute-CM, in which 421 patients received acoramidis and 211 patients received placebo. The trial allowed for patients to take Vyndamax (tafamidis) after month 12. Vyndamax was approved by the FDA in 2019 to treat adults with transthyretin mediated amyloidosis.
In the study, acoramidis met the primary endpoint, which included an analysis of all-cause mortality, then frequency of cardiovascular-related hospitalization, change from baseline in natriuretic peptide test and change from baseline in 6-minute walk distance.
The trial used the win ratio, a method for reporting composite endpoints that gives priority to certain events. Patients in these trials are matched based on risk profiles and events are compared among the pairs and assigned a “win” if they meet the endpoint.
In the trial, acoramidis achieved an 81% on survival rate compared with 74% survival rate for patients taking placebo. absolute risk reduction was 6.43% and the relative risk reduction was 25%. In terms of frequency of cardiovascular-related hospitalization, acoramidis achieved a relative risk reduction of 50%.
Additionally, acoramidis consistently led to a statistically significant treatment effect at 30 months across additional measured markers of morbidity, quality of life, and function. onally, among subjects on acoramidis that completed a Month 30 visit, 45% of subjects improved from baseline in NT-proBNP, 40% of subjects improved from baseline in 6MWD, and 13% of subjects in improved from baseline in New York Heart Association (NYHA) classification.
In the study, 37.3% of patients taking acoramidis experienced serious adverse events, and 5% of patients treated with acoramidis experienced treatment related serious adverse events that led to discontinuation
BridgeBio also presented data from the ATTRibute-CM trial at the American Heart Association (AHA) Scientific Sessions 2023 in November 2023. The trial confirmed the mechanism of acoramidis stabilizing serum TTR.
The totality of the evidence points to the potential to provide important clinical benefits over current therapeutic options for patients living with ATTR-CM, Jonathan Fox, M.D., Ph.D., president and chief medical officer of BridgeBio Cardiorenal.