To assess performance of upper limb (PUL) function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) receiving ataluren plus standard of care (SoC) in Study 041 (NCT03179631) and in the STRIDE Registry (NCT02369731).

DMD is a severe neuromuscular disorder caused by a lack of functional dystrophin. Ataluren promotes readthrough of an in-frame premature stop codon to produce full-length dystrophin and is indicated for the treatment of patients with nmDMD. Study 041 (NCT03179631) is a phase 3, double-blind, placebo-controlled 72-week trial. The STRIDE Registry (NCT02369731) is an ongoing, long-term, real-world evidence study.

In Study 041, boys with nmDMD aged ≥5 years, on a stable corticosteroid regimen, and with a 6-minute walk distance (6MWD) ≥150m were randomized 1:1, ataluren:placebo. The intention-to-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 versus 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).

In matched STRIDE versus CINRG patients (mean last assessment age, 13.1 versus 14.6), ataluren preserved hand-to-mouth function by 3.4 years (p=0.0046) as assessed by entry level items of PUL versus Brooke Scale, respectively. Median age at loss of overhead reach numerically favored STRIDE, consistent with the overall trend (15.8 versus 12.6; p=0.2872). Median age at loss of distal hand function was non-estimable for STRIDE patients.  

These results indicate that ataluren may help preserve upper limb function in patients with advanced nmDMD.