Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. In this randomized, double-blind, placebo-controlled study males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57), ataluren 20, 20, 40 mg/kg (N=60), or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-minute walk distance (6MWD) at Week 48. Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg vs placebo; the week 48 6MWD ∆=31.3 meters, post-hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg and placebo. As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need.
