Five-Year Outcomes With Delandistrogene Moxeparvovec in Patients With Duchenne Muscular Dystrophy: A Phase 1/2a Study

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.

Four ambulatory patients with DMD (≥ 4-< 8 years at enrollment) entered an open-label trial (Study 101; NCT03375164), receiving a single intravenous dose of delandistrogene moxeparvovec (2.0 × 10¹⁴ vg/kg by supercoiled quantitative polymerase chain reaction (qPCR), equivalent to 1.33 × 10¹⁴ 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.

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.

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.