Abstract Introduction Acoramidis, a highly selective, oral transthyretin (TTR) stabilizer achieves near-complete TTR stabilization, and is approved in USA and EU for treating wild-type or variant TTR amyloid cardiomyopathy (ATTR-CM) in adults. In the 30-month phase 3 ATTRibute-CM study, acoramidis treatment led to a 36% and 42% risk reduction in time to all-cause mortality (ACM) or first cardiovascular hospitalization (CVH) and ACM/recurrent CVH endpoints, respectively, compared with placebo.1,2 In the OLE study, continuous acoramidis treatment led to a 36% risk reduction in ACM at Month 42 (M42) versus those who were randomized to receive placebo and switched from placebo to acoramidis at Month 30 (P=0.006).3 No new clinically important safety issues were identified up to 42 months.3 Purpose To evaluate the long-term effects of continuous acoramidis treatment on prespecified secondary outcomes for time to CVM and time to CVM/first CVH up to M42 in OLE. Methods OLE study design has been previously described.3 Briefly, patients who received acoramidis for 30 months in ATTRibute-CM continued to receive acoramidis in OLE (continuous acoramidis) while those who received placebo switched to acoramidis (placebo to acoramidis). All patients in OLE received open-label acoramidis HCl 800 mg twice daily (corresponding to 712 mg BID active ingredient). Cause of death and suspected cardiovascular hospitalizations were adjudicated by an independent clinical events committee. CVM included cardiovascular-related death, cardiac mechanical assist device and heart transplant. CVH included cardiovascular hospitalizations (≥24 hours) and urgent visits (24 hours) for decompensation heart failure requiring IV diuretics. Modified intention-to-treat analysis was continuous from the start of ATTRibute-CM into the OLE. Time-to-event analyses for CVM or first CVH/CVM were done using a stratified Cox proportional hazards model and Kaplan–Meier curves by treatment group. Results Overall, 389 enrolled in OLE and received open-label acoramidis (263 continuous acoramidis, 126 placebo to acoramidis). At M42, CVM events (n=126) constituted the majority (76.8%) of ACM events (n=164). CVM occurred in 16.6% (68/409) of patients in the continuous acoramidis group versus 28.7% (58/202) in the placebo to acoramidis group, corresponding to a 42.1% relative risk reduction (RRR) and a HR of 0.56 (95% CI 0.389–0.791, P=0.0011) (Table, Figure A). For CVM or first CVH (Table, Figure B), at M42, continuous acoramidis treatment demonstrated a 37.5% RRR compared with placebo to acoramidis (38.4% 157/409 vs 61.4% 124/202), with a HR of 0.54 (95% CI 0.429–0.691, P0.0001). Conclusions Acoramidis treatment administered for 42 months led to a 44% hazard reduction in CVM compared with the placebo to acoramidis treatment group. These findings demonstrate the long-term clinical benefits of acoramidis, a near-complete TTR stabilizer, for reducing CVM in ATTR-CM, and the importance of early treatment.
Alexander et al. (Sat,) studied this question.