Cardiology and therapy · 2026
Cardiac Safety Outcomes in Delandistrogene Moxeparvovec Clinical Trials for Duchenne Muscular Dystrophy with Up to 5 Years of Follow-up.
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Veerapandiyan Aravindhan, Bourke John, Soslow Jonathan H, Day John W, McDonald Craig M, Mendell Jerry R, Zaidman Craig M, Mason Stefanie, Meng Jianfeng, Vivien Mark, Murphy Alexander P, Wandel Christoph, Richardson James
Аннотация
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.
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.