To assess the reliability of ataluren effectiveness data in Strategic Targeting of Registries and International Database of Excellence (STRIDE [NCT02369731]) nonsense mutation DMD (nmDMD) patients and whether mutation type is a source of bias.

STRIDE is an international, observational registry evaluating long-term effectiveness and safety of ataluren in nmDMD patients. As of 31 January 2023, STRIDE patients had a 3.5-year delay in loss of ambulation (LoA) versus a propensity-score-matched general DMD population from the CINRG Duchenne Natural History Study receiving standard of care alone.

Age at LoA was compared between (1) French DYS Registry nmDMD patients and the DYS overall DMD population; (2) CINRG nmDMD patients and CINRG patients with other DMD mutations; and (3) 3:1 propensity-score-matched STRIDE and CINRG nmDMD patients. STRIDE patients were also matched to the combined intention-to-treat populations of three ataluren randomized controlled trials (RCTs), and 48-week decline in 6-minute walk distance (6MWD) was compared between STRIDE and RCT ataluren-treated or placebo-treated patients.

Median ages at LoA were (1) 10.6 years (n=43) for DYS nmDMD patients versus 11.1 years (n=504) for the DYS overall population; (2) 11.1 years (n=16) for CINRG nmDMD patients versus 12.0 years (n=382) for CINRG patients with other DMD mutations; and (3) 13.4 years (n=48) for STRIDE versus 11.1 years (n=16) for CINRG nmDMD patients, indicating a 2.3-year delay in LoA. Mean (SD) 48-week decline in 6MWD was 25.5 (64.8) meters for STRIDE patients versus 25.7 (59.9) meters for RCT ataluren-treated patients and 35.9 (60.2) meters for placebo-treated RCT patients.

DMD mutation type did not appear to affect age at LoA. LoA was delayed in STRIDE versus CINRG nmDMD patients, and 48-week change in 6MWD was consistent between ataluren-treated STRIDE and RCT patients. Mutation type is therefore not a source of bias, indicating that STRIDE effectiveness data are reliable.