Subscribe to RSS
DOI: 10.1055/s-0036-1583648
Ataluren: Clinical Trial Results in Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
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.