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 efficacy and safety results from the placebo-controlled phase.
Boys with nmDMD aged ≥5 years, on corticosteroids, and with a 6-minute walk distance (6MWD) ≥150m were eligible. The primary objective was to determine ataluren’s effect on ambulatory function, assessed by the 6-minute walk test. Boys were randomized 1:1 to ataluren:placebo. The intention-to-treat (ITT) population comprised randomized boys who received ≥1 dose of study treatment. Predefined subgroups included boys with ≥300m 6MWD and ≥5s stand from supine (primary) and those with 300-400m 6MWD.
Ataluren and placebo groups in the ITT population and key subgroups were balanced according to enrolment age, baseline 6MWD, corticosteroid use and time to stand from supine. Significant differences in mean 6MWD change from baseline and rate of change favored ataluren in the ITT population (14.4m; 0.20m/week; p=0.0248) and 300-400m 6MWD subgroup (24.2m; 0.34m/week; p=0.0310), representing a 21% and 30% slowing of the decline rate in 6MWD in these groups, respectively. There were significant treatment benefits in time to 10% worsening of 6MWD. The number of ITT patients who lost ambulation receiving placebo was almost double that of those receiving ataluren. Ataluren was well tolerated, had no probable drug-related serious adverse events (AEs), and AE frequency (85.3%) was similar to placebo (84.7%).
Study 041 confirms ataluren’s favorable risk-benefit as shown in previous clinical and real-world evidence studies.