Background: This multicenter open-label single-arm 2-part prospective Phase 3 trial (NCT04622046) evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of acoramidis, an oral, highly selective transthyretin (TTR) stabilizer, in Japanese patients with wild-type or hereditary symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM).
Methods and results: Twenty-five patients (mean [±SD] age 76.5±6.3 years; 88% men) received acoramidis hydrochloride (800 mg twice daily) for up to 30 months. Primary endpoints were change from baseline to Month 12 in the 6-min walk distance (6MWD) and all-cause mortality and cardiovascular-related hospitalizations over 30 months. No deaths were reported over 30 months. The annualized frequency of cardiovascular-related hospitalizations was 0.133. Clinically meaningful treatment benefits were observed in least-squares mean change from baseline to Month 12 for 6MWD (-3.9 m; 95% confidence interval [CI] -22.9, 15.1 m) and to Month 30 for 6MWD (-36.2 m; 95% CI -58.5 to -13.9 m), Kansas City Cardiomyopathy Questionnaire overall score (-7.0; 95% CI -14.7, 0.8), TTR levels (9.4 mg/dL; 95% CI 6.7, 12.0 mg/dL), and median N-terminal pro B-type natriuretic peptide levels (169.5 pg/mL; interquartile range -557.0, 700.0 pg/mL). The median TTR stabilization (fluorescent probe exclusion assay) was 95.6%. Acoramidis was well tolerated.
Conclusions: Acoramidis prolongs survival, provides functional and quality-of-life benefits, and is well tolerated in Japanese patients with ATTR-CM, consistent with results from the global ATTRibute-CM Phase 3 trial.
Keywords: Acoramidis; Efficacy; Safety; Transthyretin amyloid cardiomyopathy (ATTR-CM); Transthyretin amyloidosis.
Copyright © 2026, THE JAPANESE CIRCULATION SOCIETY.