3-Year Functional Outcomes of Patients With Duchenne Muscular Dystrophy: Pooled Delandistrogene Moxeparvovec Clinical Trial Data vs External Controls

Topic:

Clinical Trials

Poster Number: P167

Author(s):

Jerry Mendell, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Anne Connolly, MD, Nationwide Children's Hospital, John Day, Stanford University, Palo Alto, CA, USA, Craig McDonald, UC Davis, Davis, CA, USA, Crystal Proud, Children's Hospital of the King's Daughters, Norfolk, VA, USA, Perry Shieh, UCLA Health, Los Angeles, CA, USA, Craig Zaidman, Washington University in Saint Louis, Saint Louis, MO, USA, Matthew Furgerson, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Kai Ding, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Carol Reid, Roche Products Ltd, Welwyn Garden City, UK, Alex Murphy, MBChB, PhD, Roche Pharmaceuticals, Jacob S. Elkins, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Louise Rodino-Kaplac, Sarepta Therapeutics, Inc, Cambridge, MA, USA

Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene therapy for Duchenne muscular dystrophy encoding an engineered, functional form of dystrophin shown to stabilize or slow disease progression. It is approved in the US and in other select countries. Here we compare 3-year functional outcomes of ambulatory patients age 4.0-8.9 y treated with delandistrogene moxeparvovec (treatment group) with those of external controls (EC), well matched using propensity-score weighting of key baseline prognostic factors.
Delandistrogene moxeparvovec data (n=50) were pooled from studies 101 (NCT03375164, n=4), 102 (NCT03769116, n=26), and ENDEAVOR Cohort 1 (NCT04626674, n=20) and compared with an EC group (n=73) using a propensity-score–weighted median regression model and a mixed-effects model for repeated measures (MMRM). Changes from baseline (CFBLs) to year 3 in the North Star Ambulatory Assessment (NSAA) total score and timed function tests (TFTs) of time to rise (TTR) from floor and 10-meter walk/run (10MWR) were assessed.
At baseline, treatment and EC groups had similar median ages (6.3 y vs 6.5 y), NSAA total scores (22.0 vs 21.0), TTRs (3.9 s vs 4.3 s), and 10MWR times (4.9 s vs 5.1 s). Median regression analyses showed clinically meaningful stabilization of disease over 3 years in the treatment group vs the EC group. Three-year CFBLs (SE) in the treatment group vs the ECs were as follows: NSAA total score, −2.55 (0.76) vs −5.55 (0.77) (between-group difference [SE]: 3.00 [0.80], P=0.0003); TTR, 2.8 (0.3) s vs 4.6 (0.3) s (between-group difference: −1.8 [0.3] s, P<.0001); 10MWR, 1.4 (0.2) s vs 1.8 (0.2) s (between-group difference: −0.4 [0.2] s, P=0.059). MMRM analyses yielded similar results and will also be presented. Our findings show that treatment with delandistrogene moxeparvovec results in long-term stabilization or slowing of disease progression compared with a rigorously matched EC group, with an increase in between-group divergence over time.