Real-World Outcomes of Delandistrogene Moxeparvovec Gene Therapy: Motor Outcomes and Emerging Safety Concerns.

Delandistrogene moxeparvovec is currently the only commercially approved gene therapy for Duchenne muscular dystrophy (DMD). Herein we report real-world data of 11 ambulatory DMD patients, ages 4-6, treated with commercial delandistrogene moxeparvovec. Patients were prospectively and uniformally monitored for 1 year post-gene-transfer for safety and motor outcomes. Nine patients experienced 15 treatment-related toxicities; 4 required escalation of corticosteroids. Side effects included gastrointestinal symptoms (n=7), liver enzyme abnormalities (n=4), acute liver injury (n=2), and troponin-I elevations (n=3). In both patients with acute liver injury, troponin-I elevations occurred in close temporal association beginning 8-9 weeks post-gene-transfer that were responsive to corticosteroids. The clinical courses of these two patients was at least partially consistent with a cellular immune response to the AAV capsid. Troponin-I elevations were asymptomatic and without acute functional changes on echocardiogram. The cohort had improvements in year 1 motor function assessments relative to baseline, including a statistically significant median 4-point increase in North Star Ambulatory Assessment score; however, important confounding factors, e.g. baseline corticosteroid use, limit interpretation and will be important to control for in future real-world data sets. Additional follow-up is required to determine long-term safety and motor outcomes with unclear generalizability of our results.