Background: Duchenne muscular dystrophy (DMD) is a fatal rare, X-linked disease characterized by progressive muscle weakness. Approximately 10–15% of DMD cases are caused by a nonsense mutation (nmDMD) in the dystrophin gene, resulting in the absence of functional dystrophin. Ataluren (10, 10, 20 mg/kg [morning, midday, and evening]) targets the underlying cause of nmDMD, enabling the formation of a full-length dystrophin.
Objective: To evaluate whether nmDMD patients receiving ataluren + standard of care (SoC; corticosteroids/palliative therapies) experienced a delay in loss of ambulation (LoA) and a slower decline in pulmonary function compared with a matched cohort of patients receiving SoC in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS; NCT00468832).
Methods: Study 019 was a phase 3, long-term (~4.5 years) safety study that enrolled nmDMD patients from prior ataluren clinical trials (NCT01557400) (N=94). Propensity score matching identified Study 019 and CINRG DNHS patients with comparable indicators of disease severity: age at first symptoms, corticosteroid type (deflazacort or other), and duration of use. Kaplan–Meier analyses estimated the age at LoA and at decline in forced vital capacity (FVC) to <60%- or <50%-predicted or <1 L.
Results: Age at LoA was delayed by ~2.5 years in nmDMD patients receiving ataluren in Study 019 compared with CINRG DNHS patients (median ages: Study 019, 15.5 years; CINRG DNHS, 13.0 years; p=0.0079 [each n=60]). In non-ambulatory patients, ataluren was associated with a delay in decline to predicted FVC <60% by ~2.5 years (median ages: Study 019, 18.1 years; CINRG DNHS, 15.5 years; p=0.0376 [each n=45]) and a trend in delay in decline to predicted FVC <50% by ~1 year.
Conclusions: Ataluren + SoC delays LoA and may delay pulmonary function decline in nmDMD patients compared with DMD patients receiving SoC, although longer follow-up will be required to more fully assess this latter outcome.