Practical considerations for delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy (DMD)


Clinical Trials

Poster Number: 105


Crystal Proud, MD, Children's Hospital of The King's Daughters, Jerry Mendell, MD, Nationwide Children's Hospital, Craig Zaidman, MD, Washington University School of Medicine and St Louis Children's Hospital, Stefanie Mason, Sarepta Therapeutics, Inc., Eddie Darton, Sarepta Therapeutics, Inc., Christoph Wandel, F. Hoffmann-La Roche Ltd, Alex Murphy, F. Hoffmann-La Roche Ltd, Eugenio Mercuri, Pediatric Neurology Institute, Fondazione Policlinico Gemelli IRCCS, Francesco Muntoni, MD, UCL Institute of Child Health and Great Ormond Street Hospital for Children, Craig McDonald, MD, University of California Davis Health

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed for targeted expression of SRP-9001 dystrophin—an engineered, shortened, functional dystrophin protein—in skeletal and cardiac muscle to address the underlying cause of Duchenne muscular dystrophy (DMD).

Objective: Outline several practical considerations for delandistrogene moxeparvovec treatment in patients with DMD.

Methods: Drawing on delandistrogene moxeparvovec clinical trial experience (Study 101 [NCT03375164], Study 102 [NCT03769116], and ENDEAVOR [Study 103; NCT04626674]), we describe the observed time-course of events, the monitoring for and management of adverse events, and mitigation strategies.

Results: The observed safety profile of delandistrogene moxeparvovec has been largely consistent (regarding types and timing of events), monitorable, and manageable. Recommendations for initiating delandistrogene moxeparvovec treatment in patients with DMD include: (1) screening for the presence of elevated levels of anti-rAAVrh74 total binding antibodies prior to infusion; (2) assessing liver function, platelet count, and troponin I levels before administration; (3) monitoring liver function weekly for the first 3 months following infusion and, if clinically indicated, continuing monitoring until results are unremarkable; (4) postponing administration for patients with acute liver disease until the issue is resolved or controlled; (5) monitoring troponin I levels pre-infusion and weekly for the first month post-infusion, continuing monitoring if clinically indicated; and (6) administering corticosteroids starting 1 day prior to infusion (for patients already on corticosteroids), and maintaining the corticosteroid regimen for a minimum of 60 days post-infusion, unless earlier tapering is clinically indicated.

Conclusions: Though the safety profile of delandistrogene moxeparvovec to date has been relatively consistent, monitorable, and manageable, appropriate mitigation of potential risks can help ensure patient safety. The practical considerations of treatment with delandistrogene moxeparvovec gene therapy provided here are based on available clinical trial data and are intended to aid physicians treating patients with DMD. Implementation of these practical considerations is recommended.

Studies 101 and 102 are sponsored and funded by Sarepta. ENDEAVOR is sponsored by Sarepta and funded by Sarepta and F. Hoffmann-La Roche.