Ataluren treatment of patients with nonsense mutation dystrophinopathy. Issue 4 (October 2014)

• Record Type: Journal Article
• Authors: 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.; FOR THE PTC124‐GD‐007‐DMD STUDY GROUP;
• Is Part Of: Muscle & nerve. Volume 50:Issue 4(2014:Oct.)
• Page Start: 477
• Page End: 487
• Publication Date: 2014-10
• Subjects: Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.24332
• Languages: English
• ISSNs: 0148-639X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <italic>Introduction</italic>: 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. <italic>Methods</italic>: 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 (<italic>N</italic> = 57); ataluren 20, 20, 40 mg/kg (<italic>N</italic> = 60); or placebo (<italic>N</italic> = 57) for 48 weeks. The primary endpoint was change in 6‐Minute Walk Distance (6MWD) at Week 48. <italic>Results</italic>: 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, <italic>post hoc P</italic> = 0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. <italic>Conclusions</italic>: 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. <italic>Muscle Nerve</italic><bold>50</bold>: 477–487, 2014</p> </abstract>