Abstract Details

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.

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