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Introduction <p>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.</p> Methods <p>We assessed cardiac safety of delandistrogene moxeparvovec in clinical trials with ≤ 5&#xa0;years of follow-up. Data were collected from clinical trials 101 (NCT03375164, <i>n</i> = 4), 102 (NCT03769116, <i>n</i> = 41), ENDEAVOR (NCT04626674, <i>n</i> = 48), and EMBARK (NCT05096221, <i>n</i> = 125), which excluded patients with left ventricular ejection fraction (LVEF) &lt; 40%. Adverse events and cardiac echocardiography were assessed regularly in all trials. Troponin&#xa0;I was assessed regularly in ENDEAVOR and EMBARK. Cardiac magnetic resonance imaging (MRI; without gadolinium enhancement) was assessed within an EMBARK substudy.</p> Results <p>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&#xa0;days after delandistrogene moxeparvovec infusion; both resolved within 3&#xa0;weeks. Except in the two myocarditis cases, troponin&#xa0;I fluctuations were asymptomatic. Thirteen patients with baseline and postbaseline echocardiography data had elevated troponin&#xa0;I at baseline; 1&#xa0;year post infusion, only one of these patients had LVEF &lt; 50%. LVEF in all four patients with 5-year follow-up remained &gt; 50%. Although cardiac MRI without gadolinium revealed no relevant differences in heart function between patients 1 or 2&#xa0;years after delandistrogene moxeparvovec versus patients 1&#xa0;year after placebo infusion, subclinical fibrosis cannot be ruled out.</p> Conclusion <p>Results from delandistrogene moxeparvovec trials with 1 to 5&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • 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

摘要

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.