Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy: Results From ATTRibute-CM and Its Open-Label Extension.

Acoramidis achieves near-complete (≥90%) TTR stabilization and showed clinical benefit in the 30-month ATTRibute-CM trial and through month 42 in the ongoing open-label extension (OLE).

Acoramidis实现了近乎完全（≥90%）的TTR稳定，并在30个月的ATTRibute-CM试验以及持续至第42个月的开放标签扩展（OLE）中显示出临床益处。

Background

To evaluate the efficacy of acoramidis in ATTRwt-CM, ATTRv-CM, and variant subgroups (p.Val142Ile and non-p.Val142Ile).

评估acoramidis在野生型ATTR心肌病（ATTRwt-CM）、遗传型ATTR心肌病（ATTRv-CM）以及变异亚组（p.Val142Ile和非p.Val142Ile）中的疗效。

DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, phase 3, randomized placebo-controlledstudy took place from April 2019 to May 2023 with ongoing OLE (month 42).

设计、设置和参与者：这项国际多中心的3期、随机安慰剂对照研究从2019年4月开始至2023年5月结束，随访至第42个月的开放标签扩展（OLE）研究仍在进行中。

ATTRibute-CM enrolled 632 participants with ATTR-CM; 611 of 632 were included in the modified intention-to-treat(mITT) population.

ATTRibute-CM研究招募了632名ATTR-CM患者；611名中的632名被纳入改良意向治疗（mITT）人群。

There were 380 participants who continued into the OLE.

有380名参与者继续进入开放标签扩展（OLE）研究。

These data were analyzed from January 2025 to July 2025.

这些数据的分析工作从2025年1月持续到2025年7月。

Methods

Oral acoramidis, 712 mg, or placebo twice daily for 30 months, followed by 12 months of open-label treatment.

口服acoramidis 712毫克，或安慰剂，每日两次，持续30个月，之后进行为期12个月的开放标签治疗。

main_outcomes_and_measures

All-cause mortality (ACM), cardiovascular-related hospitalizations (CVH), serum TTR, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, and N-terminal pro B-type natriuretic peptide in participants with ATTRwt-CM and ATTRv-CM.

在携带ATTRwt-CM和ATTRv-CM的参与者中，研究了全因死亡率（ACM）、心血管相关住院（CVH）、血清TTR、6分钟步行距离、堪萨斯城心肌病问卷总体总结评分以及N末端B型利钠肽前体。

Post-hoc analyses were conducted in variant subgroups, including p.Val142Ile.

在包括p.Val142Ile在内的变异亚组中进行了事后分析。

Results

Overall, 552 participants with wild-type ATTR-CM (mean [SD] age, 78 [6.3] years; 92.0% male and 8.0% female) and 59 participants with variant ATTR-CM (mean [SD] age, 73 [7.7] years; 77.3% male and 22.7% female) were randomized (mITT population), including 35 with p.Val142Ile.

总体而言，共有552名野生型ATTR-CM患者（平均年龄[标准差]为78[6.3]岁；92.0%为男性，8.0%为女性）和59名变异型ATTR-CM患者（平均年龄[标准差]为73[7.7]岁；77.3%为男性，22.7%为女性）被随机分配（mITT人群），其中包括35名携带p.Val142Ile突变的患者。

Consistent efficacy was observed in wild-type and variant subgroups for ACM/CVH through month 30 and ACM through month 42.

在30个月的ACM/CVH和42个月的ACM观察期内，野生型和变异型ATTR-CM亚组均显示出一致的疗效。

At month 30, acoramidis reduced the risk of ACM/first CVH vs placebo by 31% in ATTRwt-CM (hazard ratio[HR], 0.69; 95% CI, 0.52-0.90; P = .007) and by 59% in ATTRv-CM (HR, 0.41; 95% CI, 0.21-0.81; P = .01).

在第30个月时，acoramidis将ATTRwt-CM患者的全因死亡/首次心血管事件风险与安慰剂相比降低了31%（风险比[HR]，0.69；95%置信区间，0.52-0.90；P = .007），并将ATTRv-CM患者的相应风险降低了59%（HR，0.41；95%置信区间，0.21-0.81；P = .01）。

ACM was reduced through month 42 with HRs of 0.70 (95% CI, 0.50-0.98; P = .04) and 0.41 (95% CI, 0.19-0.93; P = .03) in the ATTRwt-CM and ATTRv-CM groups, respectively.

在第42个月时，ATTRwt-CM组和ATTRv-CM组的全因死亡风险分别通过风险比（HRs）降低至0.70（95%置信区间，0.50-0.98；P = .04）和0.41（95%置信区间，0.19-0.93；P = .03）。

Consistent treatment benefit was observed in participants with ATTRwt-CM and ATTRv-CM for secondary end points.

在ATTRwt-CM和ATTRv-CM的参与者中观察到对次要终点的一致治疗益处。

Within variant subgroups (p.Val142Ile vs non-p.Val142Ile), consistent treatment benefits were observed for ACM/CVH through month 30 and ACM through month 42.

在变异亚组（p.Val142Ile与非p.Val142Ile）中，通过第30个月的ACM/CVH和第42个月的ACM观察到一致的治疗益处。

conclusions_and_relevance

The beneficial effect of acoramidis was observed consistently in ATTRwt-CM and ATTRv-CM groups.

Acoramidis 的有益效果在ATTRwt-CM和ATTRv-CM组中一致观察到。

These hypothesis-generating results indicate that further studies are warranted to better characterize the therapeutic benefit of acoramidis in variant subgroups.

这些产生假设的结果表明，有必要进行进一步的研究以更好地描述Acoramidis在变异亚组中的治疗益处。

trial_registration

ClinicalTrials.gov Identifiers: NCT03860935; NCT04988386.

ClinicalTrials.gov 注册标识：NCT03860935; NCT04988386。