Ataluren preserves upper limb function in NMDMD patients from study 041, a phase 3 placebo-controlled trial, and the stride registry

*Correspondence: [e-mail].

Abstract

We assessed performance of upper limb (PUL) function in nonsense mutation Duchenne muscular dystrophy (nmDMD) patients receiving ataluren+standard of care (SoC) in Study 041 (NCT03179631), a phase 3, double-blind, placebo-controlled 72-week trial, and in the STRIDE Registry (NCT02369731), an ongoing, long-term, real-world evidence study. In Study 041, nmDMD boys aged ≥5 years, on a stable corticosteroid regimen, and with a 6-minute walk distance (6MWD) ≥150m were randomized 1:1, ataluren: placebo. The intentionto-treat (ITT) population comprised randomized boys who received at least one dose of study treatment (N=359; mean age 8.1 years); a key subgroup included those with baseline 300-400m 6MWD (n=169). STRIDE patients were propensity-score matched to patients receiving SoC alone in CINRG DNHS (NCT00468832), yielding a comparable population (N=261). Kaplan-Meier analyses estimated age at loss of upper limb function. Least-squares mean PUL total score change from baseline to week 72 (by MMRM analysis) numerically favored ataluren vs placebo (0.44, p=0.1059) in the Study 041 ITT population and was significant in the 300–400m 6MWD subgroup (1.02, p=0.0165). Inmatched STRIDE vs CINRG patients (mean last assessment age, 13.1 vs 14.6), ataluren preserved hand-to-mouth function by 3.4 years (p=0.0046) as assessed by entry level items of PUL vs Brooke Scale, respectively. Median age at loss of overhead reach numerically favored STRIDE, consistent with the overall trend (15.8 vs 12.6; p=0.2872). Median age at loss of distal hand function was non-estimable for STRIDE patients. Results indicate that ataluren may help preserve upper limb function in advanced nmDMD patients.

 

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Publication History

Article published online:
12 May 2025