Delandistrogene moxeparvovec improved the 5-year NSAA total score mean change from baseline compared with external controls (mean difference 9.8; p=0.0127).
Does delandistrogene moxeparvovec improve functional outcomes and maintain safety in patients with Duchenne muscular dystrophy?
Delandistrogene moxeparvovec demonstrated long-term safety and stabilized functional outcomes at 5 years compared to external controls in patients with Duchenne muscular dystrophy.
Mean Difference: 9.8
Absolute Event Rate: 7.5% vs -3.9%
p-value: p=0.0127
AIMS: We report 5-year results from a phase 1/2a study of delandistrogene moxeparvovec, a recombinant adeno-associated virus serotype rh74 vector-based gene therapy for Duchenne muscular dystrophy (DMD), with post hoc analyses contextualizing functional outcomes. METHODS: vg/kg by linear qPCR). Safety and functional outcomes (including North Star Ambulatory Assessment NSAA total score, time to rise TTR from floor, 10-m walk/run 10MWR time) were assessed. In post hoc analyses, functional outcomes of delandistrogene moxeparvovec-treated patients were compared with propensity-score-weighted external controls (ECs) and natural history predictions. RESULTS: No new safety signals were reported 5 years post-infusion. One patient had cardiomyopathy at year 5; however, this event was deemed unrelated to treatment. All delandistrogene moxeparvovec-treated patients (mean age, 10.2 years) remained ambulant. The 5-year NSAA total score mean change from baseline (standard deviation) for treated patients versus ECs was +7.5 (2.4) versus -3.9 (2.9) (least-squares mean between-group difference standard error: 9.8 3.5, p = 0.0127). TTR and 10MWR mean times were stable, representing clinically meaningful differences versus ECs. An increased divergence in NSAA total score from 5-year natural history predictions favoring gene therapy was also seen. DISCUSSION: Findings support the long-term, manageable safety profile of delandistrogene moxeparvovec in ambulatory patients with appropriate monitoring and demonstrate stabilization or delayed disease progression with treatment compared with matched untreated ECs.
Mendell et al. (Wed,) conducted a other in Duchenne muscular dystrophy (DMD). delandistrogene moxeparvovec vs. propensity-score-weighted external controls was evaluated on 5-year NSAA total score mean change from baseline (MD 9.8, p=0.0127). Delandistrogene moxeparvovec improved the 5-year NSAA total score mean change from baseline compared with external controls (mean difference 9.8; p=0.0127).