Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week ataluren trial in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) followed by a 72-week open-label period. Here, we describe results of a pooled analysis of ataluren muscle function efficacy results from the placebo-controlled phase of Study 041 and two previous randomized, placebo-controlled 48-week ataluren trials (Study 007 [phase 2b] and Study 020 [phase 3]).
In all three studies, patients were eligible if they were male, had phenotypic evidence of DMD based on the onset of characteristic clinical signs or symptoms, and had an nmDMD diagnosis confirmed by genetic testing. Patients were randomized 1:1 to ataluren:placebo.
Pooled efficacy results for 48-week change in 6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA) total and linear scores (where available), and timed function tests (TFTs; 10m walk/run, 4-stair ascent and 4-stair descent) are described for the overall pooled study population; and 48-week change in 6MWD for a subgroup with baseline 6MWD 300–400m, in which this endpoint is most sensitive to change over the limited time course of a clinical trial.
The overall pooled study population included 354 patients receiving ataluren and 347 patients receiving placebo. Treatment with ataluren significantly reduced mean change from baseline in all measures vs placebo for the overall population (6MWD: 19.3m, p=0.0002; NSAA total score: 1.07, p=0.0010; NSAA linear score: 2.70, p=0.0031; 10m walk/run time: -1.31s, p=0.0001; 4-stair ascent time: -1.45s (p=0.0003); 4-stair descent time: -1.54s, p=0.0003). The pooled subgroup with baseline 6MWD 300–400m included 155 patients receiving ataluren and 157 patients receiving placebo. Ataluren preserved 32.1m of 6MWD in this subgroup vs placebo (p=0.0005).
Pooled randomized, placebo-controlled clinical trial data from 701 patients demonstrate that ataluren preserves muscle function, assessed by multiple clinical meaningful endpoints, in patients with nmDMD.