Neuropediatrics 2016; 47 - P04-02
DOI: 10.1055/s-0036-1583648

Ataluren: Clinical Trial Results in Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)

U. Schara 1, C. M. McDonald 2, K. Bushby 3, M. Tulinius 4, R. Finkel 5, H. Topaloglu 6, J. W. Day 7, K. Flanigan 8, L. Lowes 8, M. Eagle 9, X. Luo 10, G. Elfring 10, H. Kroger 10, P. Riebling 10, T. Ong 10, R. Spiegel 10, S. W. Peltz 10 S.-M. Park 10for the Ataluren DMD Study Steering Committee
  • 1University of Essen, Essen, Germany
  • 2University of California Davis, Sacramento, California, USA
  • 3John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle upon Tyne, UK
  • 4University of Gothenbyrg, Queen Silvia Children's Hospital, Gothenburg, Sweden
  • 5Nemours Children's Hospital, Orlando, Florida, USA
  • 6Hacettepe University School of Medicine, Ankara, Turkey
  • 7Stanford University School of Medicine, Stanford, California, USA
  • 8Nationwide Children's Hospital, Columbus, Ohio, USA
  • 9Newcastle University, Tyne and Wear, UK
  • 10PTC Therapeutics, South Plainfield, NJ, USA

Background: Ataluren, the first drug to treat the underlying cause of nmDMD, enables ribosomal readthrough of a premature stop codon and thus produces normal-length functional dystrophin without impairing normal stop codons.

Methods: Findings on efficacy and safety/tolerability from Phase 2 and Phase 3 studies of Ataluren in nmDMD were summarized.

Results: The clinical trials were: a Phase 2a proof-of-concept study (N = 38) that demonstrated that patients with nmDMD treated for 28 days presented with increased dystrophin production in muscle biopsies following Ataluren treatment; a placebo-controlled (RCT design) Phase 2b study (N = 174) that demonstrated the treatment effect of Ataluren on a 6-minute walk distance (6MWD), on timed function tests and other physical function measures; an ongoing open-label safety long-term study (N = 108); an ongoing open-label safety/efficacy long-term study (N = 94); and a Phase 3 RCT, ACT DMD (N = 228), with a primary endpoint of change on the 6MWD over 48 weeks. The Phase 3 results demonstrated a treatment effect with Ataluren-treated patients at primary/secondary endpoints, particularly in those with a 6MWD baseline value of 300 to 400 m. Ataluren was consistently well tolerated. The results of the clinical trials will be presented in detail.

Conclusion: The totality of the results demonstrates that Ataluren enables nonsense mutation readthrough in dystrophin mRNA and produces functional dystrophin and slows disease progression.

Study supported by: PTC Therapeutics Inc.