To assess the effects of ataluren in clinically meaningful milestones in Duchenne muscular dystrophy (DMD).

Persistent 10% or 5% worsening and a 30m decline in 6-minute walk distance (6MWD) have been established as clinically meaningful milestones of disease progression in patients with DMD.

Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week ataluren trial followed by a 72-week open-label period. Eligible boys with genetically confirmed nonsense mutation DMD (nmDMD), aged ≥5 years and with a 6MWD ≥150m were randomized 1:1 to receive ataluren/placebo. The intention-to-treat population comprised boys who received ≥1 dose of study treatment. Predefined subgroups included patients with baseline 6MWD 300–400m, and patients with baseline 6MWD ≥300m and stand from supine ≥5s (primary analysis subgroup). Decline in 6MWD over 72 weeks was assessed in these populations.

In the intention-to-treat population (ataluren, n=183; placebo, n=176), ataluren significantly reduced the risk of persistent 10% and 5% worsening in 6MWD by 31% (p=0.0078) and 30% (p=0.0082), respectively, and 30m decline by 31% (p=0.0067), vs placebo. In the 6MWD 300–400m subgroup, ataluren significantly reduced the risk of persistent 10% and 5% worsening in 6MWD by 47% (p=0.0011) and 42% (p=0.0029), respectively, and 30m decline by 47% (p=0.0009), vs placebo. In the primary analysis subgroup, there was a reduced risk of 10% persistent worsening in 6MWD for patients treated with ataluren compared with placebo, this did not reach statistical significance (p=0.0659).

These results indicate that ataluren delays clinically meaningful milestones of nmDMD progression that predict ambulatory decline.