Effect of Ataluren on Age at Loss of Ambulation in Nonsense Mutation Duchenne Muscular Dystrophy: Observational Data from the STRIDE Registry

Duchenne muscular dystrophy (DMD) is a fatal, X-linked disease, characterized by progressive muscle weakness. Loss of ambulation is a major milestone in disease progression. Approximately 10–15% of cases of DMD are caused by a nonsense mutation (nmDMD) in the dystrophin gene, which leads to translation of truncated, non-functional dystrophin. Ataluren is the first approved therapy to target the underlying cause of nmDMD, enabling formation of full-length, functional dystrophin. In this study, age at loss of ambulation was evaluated in patients with nmDMD taking ataluren for at least 12 months while enrolled in the international, multi-center STRIDE (Strategic Targeting of Registries and International Datasets of Excellence) Registry (n = 207). Data were extracted from the registry on 9 July 2018. Kaplan–Meier analyses were used to investigate age at loss of ambulation. Mean (standard deviation, SD) age of registry participants starting ataluren treatment was 9.8 (3.7) and 89.2% were being treated with corticosteroids in addition to ataluren. At the date of data extraction, registry participants had a mean (SD) age of 11.6 (3.6) years. Mean (SD) exposure to ataluren within the registry was 372.6 (211.6) patient-years and 44.6% of patients had been on ataluren for more than 720 days. Mean (standard error) age at loss of ambulation in registry participants was 15.5 (0.3) years, and 50% of patients were still ambulatory at the age of 16.5 years. Safety outcomes were consistent with the known safety profile of ataluren. In summary, ataluren may delay loss of ambulation in patients with nmDMD.