Delandistrogene Moxeparvovec Shows Long-Term Safety, Tolerability in Pooled Trial Data

Most treatment-related treatment-emergent adverse events (TR-TEAEs) occurred within 90 days of infusion with delandistrogene moxeparvovec, a gene therapy indicated for Duchenne muscular dystrophy (DMD), according to a poster presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.¹ The findings suggest patients should be closely monitored in the first 90 days post treatment but that delandistrogene moxeparvovec has a manageable, consistent safety profile and is tolerable in a broad population of patients.

Delandistrogene moxeparvovec is approved in the US and other countries and has demonstrated safety and efficacy in stabilizing or slowing DMD progression, and the new study pooled data from phase 1 to phase 3 clinical trials to provide further insight into the long-term safety and tolerability of the therapy.

While patients should be closely monitored in the first 90 days post-treatment, delandistrogene moxeparvovec showed a manageable, consistent safety profile in a broad population of patients. | Image Credit: Hypnosis - stock.adobe.com

“The innate immune response to delandistrogene moxeparvovec is activated within the first hours or days post infusion, while the acquired immune response takes weeks to develop,” the study authors explained.

The study included 156 patients, 148 (95%) of whom were ambulatory and 8 (5%) of whom were nonambulatory, and the mean (range) follow-up was 2.4 (0.7-5) years. The mean age was 6.7 (3.2-20.2) years, the mean weight was 24.6 (12.5-80.1) kg, and the left ventricular ejection fraction (LVEF) range was 48.9% to 77%.

Overall, the safety profile of delandistrogene moxeparvovec was consistent across the patient population, and the most common TR-TEAEs occurring in at least 15% of patients were gastrointestinal events (69%), including vomiting (59%), nausea (38%), and upper abdominal pain (15%). Most TR-TEAEs occurred within 90 days of gene therapy administration and resolved either spontaneously or with appropriate management.

The most common treatment-related serious adverse events (TR-SAEs) were liver abnormalities, which affected 5 (3%) patients. These TR-SAEs included hypertransaminasemia (1%), liver injury (1%), and hepatotoxicity (0.6%). Additionally, increased liver investigations included gamma-glutamyl transferase, hepatic enzymes, and transaminases. Elevated liver enzymes were seen within 8 weeks of treatment, but there were no clinically significant cases after 90 days.

In 2 studies, ENDEAVOR (NCT04626674) and EMBARK (NCT05096221), troponin I levels were consistently monitored. Two patients showed early acute elevated troponin I, which was in line with a recorded myocarditis TR-SAE. The authors also noted that mild troponin I fluctuations are typical in the natural history of DMD. Across the studies, LVEF values were stable overall, they added.

“This analysis adds to the body of evidence supporting the use of delandistrogene moxeparvovec for the treatment of early and late ambulatory as well as nonambulatory patients with DMD, a patient population with a high unmet medical need,” the authors wrote. They added that the phase 3 EXPEDITION trial (NCT05967351) will continuously evaluate the safety profile of delandistrogene moxeparvovec in approximately 400 patients from previous trials for up to 5 years post infusion.

Another poster detailed the phase 4 ENDURE study (NCT06270719), which aims to provide longitudinal follow-up on the efficacy and safety of delandistrogene moxeparvovec in the real-world setting. Long-term, real-world data are crucial to expand on what has been reported in clinical trials, according to the authors.²

The observational study is enrolling patients 4 years or older and will collect medical history and prospective data on DMD treatment outcomes for up to 10 years after treatment with delandistrogene moxeparvovec or comparator therapy. Functional data and patient-reported outcomes will inform the study, which will include patients outside of delandistrogene moxeparvovec clinical trial sites to increase the generalizability of the findings.

“Existing data sources such as electronic health records or administrative claims are not suitable to adequately measure the impact of delandistrogene moxeparvovec on individuals’ DMD disease progression and safety outcomes, particularly over long periods of time,” the authors wrote. “Therefore, structured long-term follow-up in phase 4 studies provides important real-world treatment experience and data that might not be captured outside of clinical trials to inform decisions being made by families, clinicians, regulators, and payers.”

References

1. Mendell JR, McDonald CM, Mercuri EM, et al. Long-term safety and tolerability of delandistrogene moxeparvovec in Duchenne muscular dystrophy: phase 1 to phase 3 clinical trials. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Poster P89.
2. Ricchetti-Masterson KL, Santra S, Mason S, Darton E, Miller DP. ENDURE: a prospective, observational study of the comparative effectiveness and safety of delandistrogene moxeparvovec in routine clinical practice. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, TX. Poster P91.