Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
Craig Campbell, Richard J Barohn, Enrico Bertini, Brigitte Chabrol, Giacomo Pietro Comi, Basil T Darras, Richard S Finkel, Kevin M Flanigan, Nathalie Goemans, Susan T Iannaccone, Kristi J 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, Már Tulinius, Juan J Vílchez, Thomas Voit, Lee-Jen Wei, Brenda L Wong, Gary Elfring, Marcio Souza, Joseph McIntosh, Panayiota Trifillis, Stuart W Peltz, Francesco Muntoni, PTC124-GD-007-DMD Study Group, ACT DMD Study Group, Clinical Evaluator Training Groups, Craig Campbell, Richard J Barohn, Enrico Bertini, Brigitte Chabrol, Giacomo Pietro Comi, Basil T Darras, Richard S Finkel, Kevin M Flanigan, Nathalie Goemans, Susan T Iannaccone, Kristi J 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, Már Tulinius, Juan J Vílchez, Thomas Voit, Lee-Jen Wei, Brenda L Wong, Gary Elfring, Marcio Souza, Joseph McIntosh, Panayiota Trifillis, Stuart W Peltz, Francesco Muntoni, PTC124-GD-007-DMD Study Group, ACT DMD Study Group, Clinical Evaluator Training Groups
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.
Keywords: 6-minute walk distance; Duchenne muscular dystrophy; ataluren; efficacy; meta-analyses; nonsense mutation Duchenne muscular dystrophy; randomized controlled trials.
Source: PubMed