Background/Objectives: Delandistrogene moxeparvovec is an investigational rAAVrh74-based gene transfer therapy for the treatment of Duchenne muscular dystrophy (DMD) by expression of SRP-9001 dystrophin protein. An integrated analysis of 3 ongoing clinical trials for individuals with DMD (N=85) reported collective safety outcomes following the single intravenous infusion of delandistrogene moxeparvovec. Most treatment-related treatment-emergent adverse events (TEAEs) occurred within 90 days of treatment. A Delphi panel convened to formulate expert consensus recommendations for management of select TEAEs that require urgent medical intervention, including vomiting, acute liver injury (ALI), myocarditis, and immune-mediated myositis (IMM).
Methods: A panel of 12 US-based neuromuscular, hepatology, cardiology, and gene therapy experts utilized a modified Delphi process to reach consensus guidance on TEAE management. Consensus was defined as a majority of experts either agreeing or disagreeing (5-point Likert scale). Surveys were developed based on systematic literature review, data on file, clinical trial experience, and expert panel responses. All experts completed two rounds of virtual surveys followed by a live meeting.
Results: An as-needed antiemetic was recommended for vomiting. Initial mild elevations of liver laboratory tests should be assessed with repeated labs and close monitoring. If ALI is diagnosed, considerations for additional diagnostic testing, baseline corticosteroid dose adjustment, and hospitalization should be based on timing of onset and severity of symptoms. For patients with elevations in troponin I, considerations should be based on the severity of the elevation and presence of symptoms, and include corticosteroid optimization, repeated labs, electrocardiogram, echocardiogram and cardiac MRI. Experts agreed that for suspected symptomatic IMM, emergent evaluation by physical exam, labs, and additional diagnostics would be required. In addition to hospitalization and optimization of corticosteroids, non-steroidal immunosuppressive therapy could be considered depending on the clinical scenario.
Conclusions: The Delphi recommendations offer initial guidance that can be considered by clinicians for management of selected TEAEs following delandistrogene moxeparvovec therapy.