Five-year outcomes with delandistrogene moxeparvovec in patients with Duchenne Muscular Dystrophy (DMD): a phase 1/2a study

Topic:

Clinical Trials

Poster Number: P118

Author(s):

Jerry, Mendell, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Zarife Sahenk, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA, Linda P. Lowes, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA, Natalie Reash, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA, Megan A. Iammarino, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA, Lindsay N. Alfano, Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA, James Signorovitch, Analysis Group, Inc., Jim Jin, Sarepta Therapeutics, Inc, Cambridge, MA, USA, Stephanie Mason, Sarepta Therapeutics, Inc, Cambridge, MA, USA, Jacob S. Elkins, Sarepta Therapeutics, Inc, Cambridge, MA, USA, Louise R. Rodino-Klapac, Sarepta Therapeutics, Inc, Cambridge, MA, USA, Craig M. Davis, UC Davis Health, Sacramento, CA, USA

Background: Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Objective: We report 5-year safety and functional data from Study 101 (NCT03375164). Methods: Four ambulatory patients with DMD (≥4–<8 years old) received delandistrogene moxeparvovec (1.33×10^14 vg/kg) and prednisone (1 mg/kg; 30-day taper post-infusion) 1 day pre-infusion. The primary outcome was safety. Change from baseline in North Star Ambulatory Assessment (NSAA) was an efficacy outcome. The Collaborative Trajectory Analysis Project (cTAP) model was used to predict the natural history trajectory of NSAA for a group of untreated patients with matching baseline prognostic factors (including age and motor function) as those in Study 101. Results: At 5 years post-infusion, mean (range) age was 10.20 (9.07–11.12) years; all patients remained ambulant. Overall, 75 adverse events (AEs) were reported (most occurred within 70 days post-infusion); 18 treatment-related treatment-emergent AEs were reported (all mild or moderate) and the most common were vomiting and increased liver enzymes (all resolved). There were no serious AEs, clinically significant complement-mediated AEs, study discontinuations, or deaths. At 5 years, mean (standard deviation) change in NSAA total score from baseline was +7.5 (2.4) points, with a least squares mean difference vs a propensity-score-weighted external control at 4.5 years of 9.8 points (P=0.0127). cTAP modeling showed increasing divergence of treated patients’ NSAA trajectories vs their natural history predictions over the 5 years of follow-up. Conclusions: No new safety signals were reported 5 years post-infusion, supporting the manageable safety profile of delandistrogene moxeparvovec reported previously. NSAA outcomes indicate that treatment stabilizes or slows DMD disease progression at ages where decline is expected, as seen in natural history.