Effect of acoramidis on improvement or maintenance of heart failure-related health status as assessed by Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS) in ATTRibute-CM

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM), a life-threatening and progressive disease caused by destabilized transthyretin (TTR) tetramers that infiltrate the myocardium, causes a restrictive cardiomyopathy that impairs patients’ health status. Thus, a primary goal in managing ATTR-CM is to slow disease progression to preserve or improve patients’ symptoms, function, and quality of life. Acoramidis is an oral, near-complete (≥90%) TTR stabilizer, approved in the USA, Europe, Japan, and the UK for the treatment of patients with ATTR-CM. Acoramidis was shown to reduce mortality and heart failure (HF)-related health status decline, as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS), in the phase 3 ATTRibute-CM study. Given the impact of acoramidis on both mortality and health status, and that the KCCQ can only be collected in survivors, a holistic understanding of treatment benefit on both outcomes is needed to better support medical decision making. Purpose To integrate survival and HF-related health status into a single analysis to describe the efficacy of acoramidis on outcomes in patients with ATTR-CM. Methods Participants in ATTRibute-CM were randomized 2:1 to receive acoramidis HCl 800 mg or placebo twice daily for 30 months. Efficacy analyses were conducted in the mITT population (acoramidis: n=409; placebo: n=202), which consisted of all randomized participants with a baseline eGFR ≥30 mL/min/1.73 m2. At Month 30, the effect of acoramidis on KCCQ-OS was compared with placebo as: participants ‘Alive and Not Worse’ (KCCQ-OS 10-point increase from baseline) using a Cochran-Mantel-Haenszel test adjusted for randomization strata. Results At Month 30 (acoramidis: n=367; placebo: n=188), 171 (47%) acoramidis recipients were ‘Alive and Not Worse’ (KCCQ-OS