ATTRibute-CM Top-Line Results Favorable for Acoramidis

Acoramidis, an investigational compound that stabilizes transthyretin, shows promise for reducing the risk of death and CV hospitalization in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and clinical heart failure, potentially signifying that it may be a contender to join the only currently available therapy.

The top-line results from the phase III trial were announced this morning on an investor call and webcast by the manufacturer Bridgebio.

The ATTRibute-CM study randomized 421 patients to 800 mg acoramidis twice daily and 211 patients to twice-daily placebo. At 30 months, the primary hierarchical composite outcome (prioritizing all-cause mortality, followed by cumulative frequency of CV hospitalization, change from baseline in NT-proBNP, and change from baseline in 6-minute walk distance) showed greater improvement in the acoramidis group (P < 0.0001).

Additionally, all individual endpoints of the combined endpoint were significantly better in the acoramidis group than the placebo group, with the exception of all-cause mortality. On-treatment survival at 30 months was 74% in the placebo arm versus 81% in the intervention group, with the latter being close to the expected age-matched survival in patients without ATTR-CM. There also was a relative risk reduction of 50% in the frequency of CV-related hospitalization (P < 0.0001).

There were no safety signals, with similar rates of discontinuation and adverse events between the two groups.

ATTR-CM is inherited as an autosomal dominant trait caused by mutations in the transthyretin gene (TTR) or by deposits of wild-type transthyretin proteins. On the basis of positive results at 30 months in the ATTR-ACT study, the US Food and Drug Administration approved two oral formulations of tafamidis—Vyndaqel and Vyndamax (Pfizer)—to slow the progression of ATTR-CM. The drug binds to transthyretin and prevents tetramer dissociation and amyloidogenesis. The approvals came with an orphan drug designation and were considered breakthrough therapy. However, with a $225,000 price tag, tafamidis ranks as the most expensive CV drug on the market.

The primary results from ATTRibute-CM will be presented next month at the European Society of Cardiology meeting. Bridgebio said it plans to file a New Drug Application with the FDA by the end of the year.