Ataluren treatment of patients with nonsense mutation dystrophinopathy.
INTRODUCTION: 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. METHODS: 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. RESULTS: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=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. CONCLUSIONS: 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.
Bushby, K; Finkel, R; Wong, B; Barohn, R; Campbell, C; Comi, GP; Connolly, AM; Day, JW; Flanigan, KM; Goemans, N; Jones, KJ; Mercuri, E; Quinlivan, R; Renfroe, JB; Russman, B; Ryan, MM; Tulinius, M; Voit, T; Moore, SA; Lee Sweeney, H; Abresch, RT; Coleman, KL; Eagle, M; Florence, J; Gappmaier, E; Glanzman, AM; Henricson, E; Barth, J; Elfring, GL; Reha, A; Spiegel, RJ; O'donnell, MW; Peltz, SW; Mcdonald, CM; PTC124-GD-007-DMD STUDY GROUP,
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