Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disorder caused by mutations in the DMD gene that impair dystrophin production, essential for muscle fiber stability. About 10% of cases are due to nonsense mutations (nmDMD). Ataluren, a translational readthrough agent, enables ribosomes to bypass premature stop codons, leading to functional dystrophin synthesis. 

Randomized controlled trials (RCTs) were systematically searched in PubMed, Embase, and the Cochrane Central Register up to October 2025. Eligible studies included males ≥5 years with genetically confirmed nmDMD. Studies not meeting inclusion criteria or with overlapping populations were excluded. This systematic review and meta-analysis followed PRISMA and Cochrane guidelines. The primary outcomes were change in 6-Minute Walk Distance (6MWD) from baseline to week 48 and adverse events. Pooled analyses with 95% confidence intervals (CIs) were performed using RStudio software.

Three RCTs involving 695 participants (median age 8.5 years) met inclusion criteria. At week 48, ataluren showed a nonsignificant trend toward improved 6MWD compared with placebo (SMD 0.20; 95% CI −0.08 to 0.49; p = 0.09; I² = 0%). Adverse events—mainly gastrointestinal symptoms, headache, injection-site reactions, and musculoskeletal disorders—were comparable between groups (RR 1.03; 95% CI 0.85 to 1.26; p = 0.52; I² = 78%). No new safety signals were identified.

Ataluren demonstrates a favorable safety profile and a nonsignificant trend toward preserved ambulation in nmDMD. Although findings suggest potential clinical benefit, the limited number of RCTs and short follow-up durations warrant cautious interpretation. Larger, long-term, multicenter trials are required to better define ataluren’s therapeutic role in nmDMD.