Publication of positive results from phase III ATTRibute-CM study of acoramidis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the New England Journal of Medicine

ATTRibute-CM was designed to study the efficacy and safety of acoramidis, an investigational, next-generation, orally-administered, small molecule stabilizer of transthyretin (TTR).

“The consistent benefits of acoramidis treatment demonstrated by the ATTRibute-CM results, especially in the context of contemporary ATTR-CM care, are striking and encourage its potential use,” said Professor Julian Gillmore, M.D., Ph.D., head of University College London’s Centre for Amyloidosis and research lead at the UK National Amyloidosis Centre. “Given the efficacy and safety of acoramidis demonstrated in this trial, I am hopeful that it will soon be available to the benefit of the growing global population of patients diagnosed with ATTR-CM.”

The ATTRibute-CM study demonstrated a significant treatment effect of acoramidis in the primary analysis that compared, in a hierarchical manner, all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and 6-minute walk distance (6MWD). Findings presented in the NEJM support acoramidis as an effective and safe treatment option for patients with ATTR-CM and reinforce the hypothesis that greater stabilization of TTR may be associated with improved clinical outcomes.

Additional findings in the publication include: i. The majority of comparisons in the primary hierarchical analysis (58% in the associated Win Ratio) were determined by the first two components of ACM and CVH; statistical significance was also achieved on a F-S test with those two cardiovascular outcomes parameters alone. ii. Statistically significant treatment benefit was observed for change from baseline in 6MWD, Kansas City Cardiomyopathy Questionnaire (KCCQ), and serum TTR .iii. The observed 30-month survival rate of 74.3% in the placebo arm of ATTRibute-CM is greater than the observed 30-month survival rate of 70.5% in the combined tafamidis treatment arms of ATTR-ACT, the only previously reported cardiovascular outcomes study in ATTR-CM .iv. As a contemporary benchmark for placing the survival rate of 80.7% in the treatment arm of ATTRibute-CM into context, recent data from the U.S. Social Security Administration estimated 30-month survival at 85% in an age-matched cohort of the general population v. Similarly, the annualized CVH rate in the treatment arm of ATTRibute-CM of 0.29 can be viewed in the context of data on the annual overall hospitalization rate of 0.26 in the U.S. Medicare population. vi. Serum TTR was promptly and consistently elevated throughout the study in patients receiving acoramidis as a result of near-complete stabilization of the protein .vii. Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified.

“These results add to the totality of the available data supporting the concept that the greater the degree of stabilization of tetrameric TTR, the greater the observed clinical benefit,” said Jonathan Fox, M.D., Ph.D., president and chief medical officer of BridgeBio Cardiorenal. “With the submission of our NDA to register acoramidis with the FDA, and with additional regional and national regulatory submissions planned, we look forward to making acoramidis available to patients who might benefit from its demonstrated efficacy and safety.”

In July 2023, BridgeBio announced positive topline results from ATTRibute-CM. BridgeBio has also presented additional detailed results from ATTRibute-CM at the European Society of Cardiology Congress 2023 in August and at the American Heart Association Scientific Sessions 2023 in November 2023.

The Company submitted a New Drug Application to the FDA in 2023 and intends to submit additional marketing authorization applications to regulatory bodies in 2024.

See- "Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy"-Julian D. Gillmore, M.D., Ph.D., Daniel P. Judge, M.D., Francesco Cappelli, M.D., et al., for the ATTRibute-CM Investigators.-January 11, 2024 N Engl J Med 2024; 390:132-14 .DOI: 10.1056/NEJMoa2305434.