Abstract Details

Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week trial of ataluren in patients with nonsense mutation DMD (nmDMD) followed by a 72-week open-label period.

To report ataluren muscle function efficacy results from a meta-analysis of the Study 041 placebo-controlled phase and two randomized, double-blind, placebo-controlled, 48-week ataluren trials (Study 007 [phase 2b; NCT00592553] and ACT DMD [phase 3; NCT01826487]).

In all three studies, boys were eligible if they had genetically confirmed nmDMD. The meta-analysis used a weighted random-effects model and included intention-to-treat populations from Study 041, Study 007 and ACT DMD. Endpoints included changes from baseline to week 48 in 6MWD, TFTs and NSAA total and linear scores (Study 041 and ACT DMD only); mean 48-week change in 6MWD was assessed in a subgroup of patients with baseline 6MWD 300–400m.

The meta-analysis included 354 ataluren-treated patients and 347 placebo-treated patients. The differences in change from baseline to week 48 in 6MWD, TFTs and the NSAA scores between ataluren- and placebo-treated patients were statistically significant, favoring ataluren (least-squares mean difference; 6MWD: 15.8m, p=0.0032; 10m walk/run: −1.1s, p=0.0026; climb four stairs: −1.3s, p=0.0025; descend four stairs: −1.3s, p=0.0021; NSAA total score: 1.1, p=0.0010; NSAA linear score: 2.6, p=0.0036). In the 6MWD 300–400m subgroup, ataluren significantly slowed 6MWD decline by 33.7m versus placebo (p<0.0001).

In this meta-analysis of a large, heterogeneous population from the intention-to-treat populations of Study 041, Study 007 and ACT DMD, ataluren slowed decline in muscle function across multiple clinically meaningful endpoints versus placebo.