Acoramidis reduces days lost to death and/or cardiovascular-related hospitalization, preserving time alive outside the hospital in participants with ATTR-CM: results from ATTRibute-CM

Background Acoramidis is an approved, oral, near-complete (≥90%) transthyretin stabilizer for the treatment of patients with transthyretin amyloid cardiomyopathy (ATTR-CM). In the phase 3 ATTRibute-CM study, acoramidis reduced the risk of a composite of all-cause mortality or first cardiovascular-related hospitalization (CVH) through Month 30 by 36% vs placebo in participants with ATTR-CM. Days lost to death and/or CVH (DLDCVH) is a patient-centred metric that integrates mortality, frequency of CVHs and length of hospital stay into a single measure of disease burden and healthcare resource utilization, with reductions reflecting fewer inpatient bed days and more time alive outside the hospital. Purpose To assess the effect of acoramidis on reducing DLDCVH vs placebo in participants with ATTR-CM over 30 and 36 months. Methods Participants in ATTRibute-CM were randomized 2:1 to receive acoramidis HCl 800 mg or placebo twice daily for 30 months. This post hoc analysis assessed DLDCVH (using adjudicated CVH) over 30 months vs placebo in the modified intention-to-treat population. The 30-month analysis used model-based estimates for participants with 907 days of follow-up, corresponding to the maximum follow-up duration (30 months) in ATTRibute-CM. For the 36-month analysis, estimates were generated for participants with 1080 days of follow-up using two analyses. The first analysis (observed analysis) used ATTRibute-CM data plus up to 6 months of open-label extension (OLE; in which all participants received open-label acoramidis) data for all participants. The second analysis (modelled analysis) used ATTRibute-CM data plus up to 6 months of OLE data for those randomized to acoramidis, and only ATTRibute-CM data for those randomized to placebo. Results Baseline demographics and characteristics were comparable across treatment groups (N=611; acoramidis, 409; placebo, 202). The estimated mean percentage of DLDCVH was 7.5% for acoramidis and 11.7% for placebo through Month 30 (Table). The treatment effect of acoramidis translated to a mean difference of 38 fewer DLDCVH vs placebo over 30 months (2.5 years; odds ratio of zero DLDCVH=2.02 [95% CI: 1.28–2.77]; p<0.001). The effect of acoramidis over 36 months (3 years) showed a mean difference (95% CI) of 65.1 (28.4–101.9) fewer observed DLDCVH and 94.0 (48.0–139.9) fewer modelled DLDCVH, vs placebo. Conclusions In participants with ATTR-CM, acoramidis reduced DLDCVH vs placebo. Acoramidis preserved more than 1 month of time alive outside the hospital (38 days) over 30 months, with benefits extending to 65 days over 3 years using observed data and up to 94 days with modelled estimates, reflecting progressive divergence in outcomes over time. This demonstrates that acoramidis may reduce hospitalization-related healthcare costs, which are a key component of healthcare decision-making.