Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
Craig Campbell, Richard J. Barohn, Enrico Bertini, B. Chabrol, Giacomo P. Comi, Basil T. Darras, Richard S. Finkel, Kevin M. Flanigan, Nathalie Goemans, Susan T. Iannaccone, Kristi Jones, Janbernd Kirschner, Jean K. Mah, Katherine D Mathews, Craig M. McDonald, Eugenio Mercuri, Yoram Nevo, Yann Péréon, J. Ben Renfroe, Monique M. Ryan, Jacinda B. Sampson, Ulrike Schara, Thomas Sejersen, Kathryn Selby, M. Tulinius, Juan J. Vílchez, Thomas Voït, L. J. Wei, Brenda Wong, Gary Elfring, Marcio Ferreira de Souza, Joseph McIntosh, Panayiota Trifillis, Stuart W. Peltz, Francesco Muntoni, on behalf of the PTC124-GD-007-DMD Study Group, ACT DMD Study Group
Abstract
Aim: Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Materials & methods: Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] ≥300–<400 or <400 m). Meta-analyses examined 6MWD change from baseline to week 48. Results: Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2–34.1) m, p = 0.0473; ≥300–<400 m (n = 143), +43.9 (18.2–69.6) m, p = 0.0008; <400 m (n = 216), +27.7 (6.4–49.0) m, p = 0.0109. Conclusion: These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD ≥300–<400 m (the ambulatory transition phase), thereby informing future trial design.