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
C Sherrod, J Spertus, M Fontana, J Mitchell, J Tauras, H Falvey, C Chen, J F Tamby, J Fox, S Siddhanti, F Cappelli, M Hanna, B SperryAbstract
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 <5 and <10-point decrease from baseline), ‘Alive and Well’ (KCCQ-OS >60 and <10-point decrease from baseline), and ‘Alive and Better’ (KCCQ-OS >5 and >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 <5-point decrease) vs 56 (30%) placebo recipients (odds ratio [OR] 2.1; 95% CI, 1.4-3.1; P<0.001) with number needed to treat (NNT)=6 (95% CI, 4.0-11.6; Figure). Similarly, 168 (46%) acoramidis recipients and 59 (31%) placebo recipients were ‘Alive and Well’ (KCCQ-OS >60 and <10-point decrease; OR 1.9; 95% CI, 1.3-2.8; P=0.001) with NNT=7 (95% CI, 4.5-16.2). Participants who were ‘Alive and Better’ (KCCQ-OS >5-point increase) included 93 (25%) acoramidis recipients vs 26 (14%) placebo recipients (OR 2.1; 95% CI, 1.3-3.4; P = 0.0017) with NNT=9 (95% CI, 5.5-20.4).
Conclusions
In patients with ATTR-CM, acoramidis treatment was associated with a significantly greater likelihood of survival without worsening health status, as well as with improved health status compared with placebo, suggesting a clinically relevant modification of disease trajectory. These data provide an integrated assessment of health status and survival to inform medical decision making.For image description, please refer to the figure legend and surrounding text.