Meta-analyses of Ataluren in Patients with Nonsense Mutation Duchenne Muscular Dystrophy

Background/Purpose: To assess the totality of the evidence regarding the efficacy of Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) using the 6-minute walk test and timed function tests, a meta-analysis of patients pooled from the two largest, randomized, double-blind, placebo-controlled Ataluren studies was performed.

Methods: For this analysis, only patients in Study 007 who met the ACT DMD inclusion criteria were combined with patients in ACT DMD. Males aged 7 to 16 years with nmDMD, baseline 6-minute walk distance (6MWD) of ≥150 m and ≤80% of predicted, and ≥6 months of steroid use received Ataluren 10, 10, 20 mg/kg or placebo administered three times daily for 48 weeks. The primary endpoint in both trials was change in 6MWD at week 48.

Results: Overall, 291 patients were included in this analysis (ACT DMD: Ataluren, n = 114; placebo, n = 114; Ph2b: Ataluren, n = 32; placebo, n = 31). A statistically significant 21.1-m benefit in 6MWD (p = 0.0193) was observed in patients who received Ataluren compared with placebo. Timed function tests also showed statistically significant improvement with Ataluren over placebo: time to walk/run 10 m (−1.4 seconds; p = 0.0251), time to climb four stairs (−1.6 seconds; p = 0.0184), and time to descend four stairs (−2.0 seconds; p = 0.0044). Analysis of all patients obtained similar results (p < 0.05 for all endpoints).

Conclusion: This meta-analysis of 291 patients with nmDMD across two clinical trials demonstrated that patients who received Ataluren over 48 weeks obtained a statistically significant clinical benefit as measured by 6MWD and timed function tests compared with placebo.