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Ataluren treatment of patients with nonsense mutation dystrophinopathy
Author(s) -
Bushby Katharine,
Finkel Richard,
Wong Brenda,
Barohn Richard,
Campbell Craig,
Comi Giacomo P.,
Connolly Anne M.,
Day John W.,
Flanigan Kevin M.,
Goemans Nathalie,
Jones Kristi J.,
Mercuri Eugenio,
Quinlivan Ros,
Renfroe James B.,
Russman Barry,
Ryan Monique M.,
Tulinius Mar,
Voit Thomas,
Moore Steven A.,
Lee Sweeney H.,
Abresch Richard T.,
Coleman Kim L.,
Eagle Michelle,
Florence Julaine,
Gappmaier Eduard,
Glanzman Allan M.,
Henricson Erik,
Barth Jay,
Elfring Gary L.,
Reha Allen,
Spiegel Robert J.,
O'donnell Michael W.,
Peltz Stuart W.,
Mcdonald Craig M.
Publication year - 2014
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.24332
Subject(s) - nonsense mutation , medicine , placebo , duchenne muscular dystrophy , clinical endpoint , pediatrics , surgery , clinical trial , mutation , genetics , biology , pathology , missense mutation , alternative medicine , gene
: 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. Muscle Nerve 50 : 477–487, 2014