Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.

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.

Acoramidis是一种已批准的治疗药物，能够实现近乎完全（≥90%）的sTTR稳定。在ATTRibute-CM研究中，该药物在第30个月时显示出临床益处，并在开放标签扩展（OLE）研究中持续至第42个月。然而，更长期的疗效持续性尚未报道。

Background

To evaluate the long-term efficacy and safety of acoramidis through month 54.

通过第54个月评估acoramidis的长期疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: This OLE of the ATTRibute-CM randomized clinical trial is an international, multicenter, ongoing OLE study.

设计、设置和参与者：这是ATTRibute-CM随机临床试验的开放标签延伸（OLE）研究，是一项国际多中心的持续进行中的开放标签延伸研究。

Data accumulated between October 2021 and April 2025 through month 24 of the OLE (month 54) are reported.

报告了2021年10月至2025年4月期间，通过开放标签扩展期（OLE）第24个月（即第54个月）累积的数据。

Participants (aged 18-90 years) who completed ATTRibute-CM and met the OLE eligibility criteria were invited to enroll in the OLE.

已完成ATTRibute-CM研究并符合开放标签扩展期（OLE）资格标准的参与者（年龄在18至90岁之间）被邀请参加OLE。

Data were analyzed from May 2025 through November 2025.

数据分析从2025年5月持续到2025年11月。

Methods

All OLE participants received open-label oral acoramidis, 800 mg, twice daily.

所有开放标签扩展研究（OLE）参与者每天两次口服800毫克的acoramidis。

Acoramidis recipients from ATTRibute-CM continued therapy (continuous acoramidis) and placebo recipients switched to acoramidis (placebo to acoramidis).

ATTRibute-CM 的 Acoramidis 接受者继续接受治疗（持续使用 Acoramidis），而安慰剂接受者转为使用 Acoramidis（从安慰剂转为 Acoramidis）。

main_outcomes_and_measures

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.

主要结果是两组的全因死亡（ACM）、心血管相关死亡（CVM）和首次心血管住院（CVH）的时间事件，对两组均进行了评估。

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.

疾病进展的生物标志物（N末端前体B型利钠肽[NT-proBNP]）、sTTR、功能能力（6分钟步行距离[6MWD]）以及与心力衰竭相关健康状况（堪萨斯城心肌病问卷-总体摘要[KCCQ-OS]评分）被分析。

Results

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.

在ATTRibute-CM研究中，632名参与者被随机分配接受阿科拉米司（n = 421）或安慰剂（n = 211）；平均（标准差）年龄为77.3（6.6）岁，62名参与者（9.8%）为女性。

Overall, 389 participants enrolled in the OLE (263 in the continuous acoramidis group; 126 in the placebo-to-acoramidis group).

总体而言，共有389名参与者参与了开放标签扩展研究（OLE）（263名在连续使用acoramidis组；126名在安慰剂转为acoramidis组）。

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.

连续使用acoramidis治疗在54个月内降低了全因死亡（ACM）的风险（风险比[HR]，0.55；95%置信区间[CI]，0.42-0.74；P < .001）和心血管死亡（CVM）的风险（HR，0.51；95% CI，0.36-0.71；P < .001），在所有预先设定的亚组中疗效一致。

Continuous acoramidis reduced time to first CVH (HR, 0.53; 95% CI, 0.42-0.69; P < .001) through month 54.

连续使用阿科拉米迪可缩短首次心血管事件发生时间（风险比，0.53；95% 置信区间，0.42-0.69；P < .001）直至第54个月。

Through month 54, continuous acoramidis stabilized increases in NT-proBNP, sustained higher sTTR levels, and stabilized KCCQ-OS score and 6MWD.

在第54个月期间，连续使用阿科拉米迪稳定了NT-proBNP的增加，维持了较高的sTTR水平，并稳定了KCCQ-OS评分和6分钟步行距离（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.

在第30个月从安慰剂转换到acoramidis治疗与NT-proBNP和KCCQ-OS评分的稳定以及sTTR和6MWD的改善相关，直至第54个月。

No new long-term safety concerns were identified.

未发现新的长期安全问题。

conclusions_and_relevance

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.

在这项ATTRibute-CM随机临床试验的事后观察研究中，早期和持续的acoramidis治疗导致了从第54个月开始的全因死亡率(ACM)、心血管死亡率(CVM)和首次心血管住院(CVH)的持续增量降低。

These findings support the importance of early and continuous long-term treatment with acoramidis in ATTR-CM.

这些发现支持了在ATTR-CM中早期和持续长期使用acoramidis治疗的重要性。

trial_registration

ClinicalTrials.gov Identifier: NCT04988386.

临床试验注册号：NCT04988386。