Cardiac Safety Outcomes in Delandistrogene Moxeparvovec Clinical Trials for Duchenne Muscular Dystrophy with Up to 5 Years of Follow-up.

IF 3.2 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiology and Therapy Pub Date : 2026-09-01 Epub Date: 2026-07-01 DOI:10.1007/s40119-026-00457-5

Aravindhan Veerapandiyan, John Bourke, Jonathan H Soslow, John W Day, Craig M McDonald, Jerry R Mendell, Craig M Zaidman, Stefanie Mason, Jianfeng Meng, Mark Vivien, Alexander P Murphy, Christoph Wandel, James Richardson

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引用次数: 0

Abstract

Introduction: In patients with Duchenne muscular dystrophy (DMD), the gene transfer therapy delandistrogene moxeparvovec delivers a functional form of dystrophin, which has been shown to stabilize or slow disease progression.

Methods: We assessed cardiac safety of delandistrogene moxeparvovec in clinical trials with ≤ 5 years of follow-up. Data were collected from clinical trials 101 (NCT03375164, n = 4), 102 (NCT03769116, n = 41), ENDEAVOR (NCT04626674, n = 48), and EMBARK (NCT05096221, n = 125), which excluded patients with left ventricular ejection fraction (LVEF) < 40%. Adverse events and cardiac echocardiography were assessed regularly in all trials. Troponin I was assessed regularly in ENDEAVOR and EMBARK. Cardiac magnetic resonance imaging (MRI; without gadolinium enhancement) was assessed within an EMBARK substudy.

Results: Of 218 patients (baseline mean age [range], 6.4 [3.2-20.2] years; mean LVEF [range], 63.8% [48.9-78.0%]), 210 (96%) were ambulatory; 216 received delandistrogene moxeparvovec treatment. Two myocarditis cases were reported within 4 days after delandistrogene moxeparvovec infusion; both resolved within 3 weeks. Except in the two myocarditis cases, troponin I fluctuations were asymptomatic. Thirteen patients with baseline and postbaseline echocardiography data had elevated troponin I at baseline; 1 year post infusion, only one of these patients had LVEF < 50%. LVEF in all four patients with 5-year follow-up remained > 50%. Although cardiac MRI without gadolinium revealed no relevant differences in heart function between patients 1 or 2 years after delandistrogene moxeparvovec versus patients 1 year after placebo infusion, subclinical fibrosis cannot be ruled out.

Conclusion: Results from delandistrogene moxeparvovec trials with 1 to 5 years of follow-up suggest a manageable cardiac safety profile in this study population of predominantly younger, ambulatory patients with DMD who had no signs of persistent treatment-related cardiac injury.

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Delandistrogene Moxeparvovec治疗杜氏肌营养不良临床试验的心脏安全结局长达5年的随访。

在Duchenne肌营养不良症（DMD）患者中，基因转移疗法delandistrogene moxeparvovec提供了一种功能性的肌营养不良蛋白，已被证明可以稳定或减缓疾病进展。方法：我们在临床试验中评估德兰替罗原莫舍帕韦克的心脏安全性，随访≤5年。数据来自临床试验101 （NCT03375164, n = 4）、102 （NCT03769116, n = 41）、ENDEAVOR （NCT04626674, n = 48）和EMBARK (NCT05096221, n = 125)，其中排除了左心室射血分数（LVEF）患者。结果：218例患者（基线平均年龄[范围]6.4[3.2-20.2]岁；平均LVEF[范围]63.8%[48.9-78.0%]），210例（96%）是可移动的；216例接受德兰异丙基莫西法韦治疗。2例心肌炎患者在德兰异丙基莫舍帕韦输注后4天内报告；两例均在3周内痊愈。除2例心肌炎病例外，肌钙蛋白I波动无症状。13例患者的基线和基线后超声心动图数据在基线时肌钙蛋白I升高；输注1年后，这些患者中只有1例LVEF达到50%。虽然不加钆的心脏MRI显示，在服用德兰非甾体莫西帕韦克1年或2年的患者与服用安慰剂1年的患者之间，心功能没有相关差异，但不能排除亚临床纤维化。结论：delandistrogene moxeparvovec 1 - 5年随访的结果表明，在研究人群中，主要是年轻的、没有持续治疗相关心脏损伤迹象的动态DMD患者，心脏安全性是可控的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiology and Therapy CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Cardiology and Therapy is an international, open access, peer reviewed (single-blind), rapid-publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of cardiovascular therapies and interventions, including devices. Studies relating to diagnosis and diagnostics, pharmacoeconomics, public health, quality of life, as well as patient care, management and education are also encouraged. Areas of focus include, but are not limited to, ischaemic heart disease and acute cardiac care, myocardial, valvular, pericardial and congenital heart disease, vascular and pulmonary disease (including hypertension), arrhythmias, heart failure, non-invasive diagnostic techniques, and invasive and interventional cardiology as well as cardiovascular surgery. 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