Efficacy of Acoramidis in Adults With Transthyretin Amyloid Cardiomyopathy　― Propensity Score Comparison Between a Single-Arm Open-Label Phase 3 Trial in Japan and a Global Double-Blind Phase 3 Trial ―

Background: Acoramidis is an oral, highly selective transthyretin (TTR) stabilizer approved for transthyretin amyloid cardiomyopathy (ATTR-CM). This analysis compared efficacy outcomes over a 30-month period between acoramidis-treated patients from the Phase 3 Japan Study (NCT04622046) with propensity score (PS)-matched placebo patients from the global ATTRibute-CM trial (NCT03860935). Methods and Results: In the modified intention-to-treat population, PS matching using an optimal 1 : 2 matching ratio (absolute standardized mean difference ≤0.25 for all covariates) was used to match 25 acoramidis-treated Japanese patients with 50 placebo-treated patients from ATTRibute-CM. Baseline covariates for PS matching were age, sex, body mass index, New York Heart Association class, ATTR-CM genetic status, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and 6-min walk distance (6MWD). There were no deaths reported with acoramidis over 30 months, compared with 24% all-cause mortality events among PS-matched placebo patients. There was an 81% reduction in the annualized frequency of cardiovascular-related hospitalizations with acoramidis compared with the PS-matched placebo group. The degree of worsening in 6MWD, Kansas City Cardiomyopathy Questionnaire overall score, and NT-proBNP was less with acoramidis than with placebo. Acoramidis produced a sustained increase in TTR levels and median TTR stabilization assessed using a fluorescent probe exclusion assay. Conclusions: Clinically meaningful benefits were observed favoring acoramidis over placebo (ATTRibute-CM trial) in survival, cardiovascular-related hospitalizations, functional endpoints, and quality of life assessments.