Ataluren treatment of patients with nonsense mutation dystrophinopathy

FOR THE PTC124-GD-007-DMD STUDY GROUP

Research output: Contribution to journalArticle

192 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)477-487
Number of pages11
JournalMuscle and Nerve
Volume50
Issue number4
DOIs
StatePublished - Oct 1 2014

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Nonsense Codon
Placebos
Inborn Genetic Diseases
Therapeutics
Investigational Drugs
Orphaned Children
Muscular Diseases
Drug Delivery Systems
ataluren
Double-Blind Method
Pharmaceutical Preparations

Keywords

  • Duchenne muscular dystrophy
  • Genetic
  • Nonsense mutation
  • Orphan
  • Pediatric

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Ataluren treatment of patients with nonsense mutation dystrophinopathy. / FOR THE PTC124-GD-007-DMD STUDY GROUP.

In: Muscle and Nerve, Vol. 50, No. 4, 01.10.2014, p. 477-487.

Research output: Contribution to journalArticle

FOR THE PTC124-GD-007-DMD STUDY GROUP. / Ataluren treatment of patients with nonsense mutation dystrophinopathy. In: Muscle and Nerve. 2014 ; Vol. 50, No. 4. pp. 477-487.
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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.",
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AU - Bushby, Katharine

AU - Finkel, Richard

AU - Wong, Brenda

AU - Barohn, Richard

AU - Campbell, Craig

AU - Comi, Giacomo P.

AU - Connolly, Anne M.

AU - Day, John W.

AU - Flanigan, Kevin M.

AU - Goemans, Nathalie

AU - Jones, Kristi J.

AU - Mercuri, Eugenio

AU - Quinlivan, Ros

AU - Renfroe, James B.

AU - Russman, Barry

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AU - Tulinius, Mar

AU - Voit, Thomas

AU - Moore, Steven A.

AU - Lee Sweeney, H.

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AU - Coleman, Kim L.

AU - Eagle, Michelle

AU - Florence, Julaine

AU - Gappmaier, Eduard

AU - Glanzman, Allan M.

AU - Henricson, Erik

AU - Barth, Jay

AU - Elfring, Gary L.

AU - Reha, Allen

AU - Spiegel, Robert J.

AU - O'donnell, Michael W.

AU - Peltz, Stuart W.

AU - McDonald, Craig M.

AU - Kornberg, A. J.

AU - Wray, A.

AU - Carroll, K.

AU - Kennedy, R.

AU - Villano, D.

AU - de Valle, K.

AU - North, K. N.

AU - Dexter, M.

AU - Wicks, S.

AU - Rose, K.

AU - Buyse, G. M.

AU - van den Hauwe, M.

AU - Vrijsen, B.

AU - Janmohammad, A.

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N2 - 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.

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KW - Duchenne muscular dystrophy

KW - Genetic

KW - Nonsense mutation

KW - Orphan

KW - Pediatric

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