Safety and Early Treatment Outcomes following Delandistrogene Moxeparvovec Gene Therapy for Duchenne Muscular Dystrophy at a Single Center

Topic:

Clinical Management

Poster Number: P65

Author(s):

Dennis Keselman, MD, Children's Hospital of Philadelphia, Tiffany Seneviratne, Children's Hospital of Philadelphia, Juliana Small, PhD, Children's Hospital of Philadelphia, Sarah McCague, MS, Children's Hospital of Philadelphia, Sabrina Yum, M.D., Children's Hospital of Philadelphia, Tamir Diamond, MD, Children's Hospital of Philadelphia, Carol Wittlieb-Weber, MD, Children's Hospital of Philadelphia, Susan Matesanz, MD, Children's Hospital of Philadelphia

BACKGROUND AND METHODS: The first FDA-approved gene therapy for Duchenne muscular dystrophy (DMD), delandistrogene moxeparvovec, was licensed in June 2023 for ambulatory patients aged 4-5 and expanded to all patients aged 4+ in June 2024, though only studied in patients meeting strict trial criteria. Here, we report safety and early functional outcomes in this retrospective case series of 11 patients treated with delandistrogene moxeparvovec at a large treatment center between June 2023-2024. Nine patients had follow-up through at least 6 months post-treatment, with two followed through 12 months.

RESULTS: Mean (SD) baseline function was as follows: North Star Ambulatory Assessment (NSAA): 20.1 (6.3), time-to-rise (TTR): 7.5s (7.1), 10m walk/run (10MWR): 6.2s (1.8), 4-stair-climb (4SC): 6.9s (5.5), 100m-run (100MR): 77.8s (26.0). Notably, baseline status of 6 patients differed from clinical trial inclusion criteria: NSAA < 16 (n=3), TTR > 5s (n=5), NSAA ≥30 (n=1), corticosteroid-naive status (n=5), and severe behavioral concerns (n=2). Patients with 6-month functional scores post-treatment showed mean (SD) improvement from baseline in: NSAA: +3.7 (3.4), TTR: -3.9s (5.9), 10MWR: -1.4s (1.8), 4SC: -3.1s (4.4), 100MR: -20.0s (16.0), and those with 12-month data continued to show improvement. Nine of 11 patients experienced at least 1 adverse reaction, most commonly gastrointestinal symptoms (73%). One patient had a mild infusion reaction. Three patients developed hepatitis necessitating increased corticosteroid. Of this group, one patient required admission for IV methylprednisolone for elevated GGT and persistently elevated troponin-I four months post-treatment. Baseline and follow-up echocardiograms were normal in all patients; two had persistent troponin elevations. Three additional patients visited the ER but did not require admission.

CONCLUSIONS: Treatment with delandistrogene moxeparvovec in this real-world cohort, over 50% of whom did not meet clinical trial inclusion criteria, was generally well tolerated. Ongoing, longer-term efficacy data is needed, but 6-month outcome data showed benefit.