Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.
Prem, S., M, C.S.A., D, G.J., Nitasha, S., P, J.D., Francesco, C., K, S.L., Richard, W., Olakunle, A., Laura, O., Kunal, B., Kuangnan, X., Adam, C., Chris, C., Heather, F., Lucia, P.M., Jean-François, T., Uma, S., C, F.J., . . . K, C.R. (2026). Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2026.0819
Prem S, M CSA, D GJ, Nitasha S, P JD, Francesco C, et al. Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.. JAMA Cardiol. 2026; doi: 10.1001/jamacardio.2026.0819
Prem S, M CSA, D GJ, et al. Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.[J]. JAMA Cardiol. 2026. DOI: 10.1001/jamacardio.2026.0819.
@article{prem2026,
author = {Soman Prem and Cuddy Sarah A M and Gillmore Julian D and Sarswat Nitasha and Judge Daniel P and Cappelli Francesco and Stern Lily K and Wright Richard and Akinboboye Olakunle and Obici Laura and Bhatt Kunal and Xiong Kuangnan and Castaño Adam and Chen Chris and Falvey Heather and Pecoraro Maria Lucia and Tamby Jean-François and Sinha Uma and Fox Jonathan C and Shah Keyur and Grodin Justin L and Ambardekar Amrut V and Alexander Kevin M and Khouri Michel G and Cheng Richard K},
title = {Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.},
journal = {JAMA Cardiol},
year = {2026},
doi = {10.1001/jamacardio.2026.0819},
note = {PMID: 41911489},
}
TY - JOUR AU - Soman Prem AU - Cuddy Sarah A M AU - Gillmore Julian D AU - Sarswat Nitasha AU - Judge Daniel P AU - Cappelli Francesco AU - Stern Lily K AU - Wright Richard AU - Akinboboye Olakunle AU - Obici Laura AU - Bhatt Kunal AU - Xiong Kuangnan AU - Castaño Adam AU - Chen Chris AU - Falvey Heather AU - Pecoraro Maria Lucia AU - Tamby Jean-François AU - Sinha Uma AU - Fox Jonathan C AU - Shah Keyur AU - Grodin Justin L AU - Ambardekar Amrut V AU - Alexander Kevin M AU - Khouri Michel G AU - Cheng Richard K TI - Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial. T2 - JAMA Cardiol PY - 2026 DO - 10.1001/jamacardio.2026.0819 AN - PMID:41911489 ER -
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disorder caused by destabilization of serum transthyretin (sTTR). Acoramidis, an approved therapy that achieves near-complete (≥90%) sTTR stabilization, demonstrated clinical benefit through month 30 in ATTRibute-CM, which was incremental through month 42 in the open-label extension (OLE); however, the longer-term durability of outcomes has not been reported. To evaluate the long-term efficacy and safety of acoramidis through month 54. This OLE of the ATTRibute-CM randomized clinical trial is an international, multicenter, ongoing OLE study. Data accumulated between October 2021 and April 2025 through month 24 of the OLE (month 54) are reported. Participants (aged 18-90 years) who completed ATTRibute-CM and met the OLE eligibility criteria were invited to enroll in the OLE. Data were analyzed from May 2025 through November 2025. All OLE participants received open-label oral acoramidis, 800 mg, twice daily. Acoramidis recipients from ATTRibute-CM continued therapy (continuous acoramidis) and placebo recipients switched to acoramidis (placebo to acoramidis). The primary outcome was time to event for all-cause mortality (ACM), cardiovascular-related mortality (CVM), and first cardiovascular hospitalization (CVH), which was assessed for both groups. Biomarkers of disease progression (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), sTTR, functional capacity (6-minute walk distance [6MWD]), and heart failure-related health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary [KCCQ-OS] score) were analyzed. In ATTRibute-CM, 632 participants were randomized to receive acoramidis (n = 421) or placebo (n = 211); mean (SD) age was 77.3 (6.6) years, and 62 participants (9.8%) were female. Overall, 389 participants enrolled in the OLE (263 in the continuous acoramidis group; 126 in the placebo-to-acoramidis group). Continuous acoramidis treatment reduced risks of ACM (hazard ratio [HR], 0.55; 95% CI, 0.42-0.74; P < .001) and CVM (HR, 0.51; 95% CI, 0.36-0.71; P < .001) through month 54, with consistent efficacy across all prespecified subgroups. Continuous acoramidis reduced time to first CVH (HR, 0.53; 95% CI, 0.42-0.69; P < .001) through month 54. Through month 54, continuous acoramidis stabilized increases in NT-proBNP, sustained higher sTTR levels, and stabilized KCCQ-OS score and 6MWD. Switching from placebo to acoramidis at month 30 was associated with stabilization of NT-proBNP and KCCQ-OS score and improvements in sTTR and 6MWD through month 54. No new long-term safety concerns were identified. In this OLE of the ATTRibute-CM randomized clinical trial, early and continuous acoramidis treatment resulted in sustained incremental reductions in ACM, CVM, and first CVH through month 54. These findings support the importance of early and continuous long-term treatment with acoramidis in ATTR-CM. ClinicalTrials.gov Identifier: NCT04988386.