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.
Ataluren treatment of patients with nonsense mutation dystrophinopathy / K. Bushby, R. Finkel, B. Wong, R. Barohn, C. Campbell, G.P. Comi, A.M. Connolly, J.W. Day, K.M. Flanigan, N. Goemans, K.J. Jones, E. Mercuri, R. Quinlivan, J.B. Renfroe, B. Russman, M.M. Ryan, M. Tulinius, T. Voit, S.A. Moore, H. Lee Sweeney, R.T. Abresch, K.L. Coleman, M. Eagle, J. Florence, E. Gappmaier, A.M. Glanzman, E. Henricson, J. Barth, G.L. Elfring, A. Reha, R.J. Spiegel, M.W. O'Donnell, S.W. Peltz, C.M. Mcdonald. - In: MUSCLE & NERVE. - ISSN 0148-639X. - 50:4(2014), pp. 477-487.
Ataluren treatment of patients with nonsense mutation dystrophinopathy
G.P. Comi;
2014
Abstract
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.File | Dimensione | Formato | |
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