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 the effects of ataluren on motor function, assessed by the North Star Ambulatory Assessment (NSAA).
Boys with nmDMD aged ≥5 years, on corticosteroids for ≥12 months and with a 6-minute walk distance (6MWD) ≥150m were eligible and randomized 1:1 to ataluren:placebo. The intention-to-treat (ITT) population comprised randomized boys who received ≥1 dose of study treatment. Key subgroups included boys with ≥300m 6MWD and ≥5s supine-to-stand time and those with 300-400m 6MWD. Change from baseline to week 72 NSAA total score was a secondary endpoint. A revised NSAA was used consisting of 16 activities (head lift was excluded), each scored as 0, 1, or 2, and summed to give a total score. Transformation of the total score to a linear scale was additionally performed.
Ataluren and placebo groups were balanced according to enrollment age, baseline 6MWD, corticosteroid use and supine-to-stand time. A significant difference between the ataluren and placebo groups, favoring ataluren, was observed in the ITT population for both the total and linear NSAA score change from baseline (0.9, p=0.0235 and 2.3, p=0.0246, respectively). This was consistent with results for the primary endpoint of slope change in 6MWD. The relative declines in total and linear scores were 19.0% and 19.3% smaller in the ataluren group than in the placebo group. In both key subgroups, the difference in change from baseline in NSAA score numerically favored treatment with ataluren compared with placebo, while a significant difference was observed for the 300-400m 6MWD subgroup (3.3, p=0.0419).
These results from Study 041 demonstrate that ataluren preserves the ability to perform the NSAA, and therefore preserves motor function in patients with nmDMD.