Background

Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed.

Objectives

The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655).

Methods

After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms.

Results

Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: −35.6 ± 32.6 mm Hg; Valsalva: −45.3 ± 35.9 mm Hg), N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels (median: −480 ng/L; Q1-Q3: −1,104 to −179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events.

Conclusions

Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.

中文翻译：

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Mavacamten 治疗症状性梗阻性肥厚性心肌病：MAVA-LTE 研究、EXPLORER-LTE 队列的中期结果

背景

需要评估 mavacamten 治疗症状性梗阻性肥厚型心肌病的长期安全性和有效性的数据。

目标

作者试图评估 MAVA-LTE 的 EXPLORER-长期扩展 (LTE) 队列的中期结果（Mavacamten 在已完成 EXPLORER-HCM 的成人中的长期安全扩展研究；NCT03723655 ）。

方法

在母公司 EXPLORER-HCM（在成人症状性梗阻性肥厚性心肌病中评估 Mavacamten [MYK-461] 的临床研究；NCT03470545）结束后，退出 mavacamten 或安慰剂后，患者可以参加 MAVA-LTE。患者接受 mavacamten 5 mg 每日一次；根据现场读取的超声心动图进行调整。

结果

2019年4月9日至2021年3月5日期间，244名符合条件的患者中有231名（94.7%）参加了MAVA-LTE（平均年龄：60岁；39%为女性）。截至数据截止（2021 年 8 月 31 日），217 名患者 (93.9%) 仍在接受治疗（研究中位时间：62.3 周；范围：0.3-123.9 周）。48 周时，患者左心室流出道 (LVOT) 梯度有所改善（相对于基线的平均变化 ± SD：静息：-35.6 ± 32.6 mm Hg；Valsalva：-45.3 ± 35.9 mm Hg），N 端 pro-B-型利钠肽 (NT-proBNP) 水平（中位数：−480 ng/L；Q1-Q3：−1,104 至 −179 ng/L）和 NYHA 功能分级（67.5% 改善≥1 级）。达到该时间点的患者的 LVOT 梯度和 NT-proBNP 降低持续了 84 周。在超过 315 患者年的暴露中，8 名患者经历了心力衰竭的不良事件，21 名患者发生了房颤的不良事件，其中 11 名患者既往没有房颤病史。12 名患者 (5.2%) 现场读取的超声心动图左心室射血分数出现短暂降低<50%，导致治疗暂时中断；全部康复了。十名患者因治疗中出现的不良事件而停止治疗。

结论

Mavacamten 治疗在 LVOT 梯度、NT-proBNP 水平和 NYHA 功能分级方面显示出临床上重要且持久的改善，与 EXPLORER-HCM 一致。在中位 62 周的随访中，Mavacamten 治疗的耐受性良好。