Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow Duchenne muscular dystrophy (DMD) progression; it is approved in the United States and in other select countries. Here we summarize pooled safety outcomes from clinical trials of delandistrogene moxeparvovec with up to 5 years’ follow-up as of January 15, 2024.
Data were collected from studies 101 (NCT03375164), 102 (NCT03769116), ENDEAVOR Cohorts 1-5b (NCT04626674), and EMBARK Part 1 (NCT05096221). In total, 156 patients were included (age: mean [range], 6.7 [3.2-20.2] years; weight: mean [range], 24.6 [12.5-80.1] kg; left ventricular ejection fraction: range, 48.9%-77%; ambulatory: n [%], 148 [95%]). The treatment-related, treatment-emergent adverse events (TR-TEAEs) that occurred most frequently (≥15% of patients) were vomiting, nausea, decreased appetite, increased glutamate dehydrogenase, and upper abdominal pain. Most TR-TEAEs occurred within 90 days of treatment administration and resolved spontaneously or with appropriate management. Reported treatment-related serious AEs were liver abnormalities (8 events), rhabdomyolysis (4), vomiting (3), myocarditis (2), immune-mediated myositis (2), nausea (1), and pyrexia (1). Safety appeared to be consistent between patients who were ambulatory and 3-7 years of age (n=141), ambulatory and 8-13 years of age (n=7), or non-ambulatory and 9-21 years of age (n=8). There have been no deaths, study discontinuations, or clinically significant AEs related to complement activation as of January 15, 2024.
Overall, delandistrogene moxeparvovec has a manageable safety and tolerability profile across a broad population of patients with DMD, regardless of age, weight, or stage of disease.
These data were previously presented at the World Muscle Society Annual Congress; October 8-12, 2024.