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Meta-Analysis
27 August 2020

Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy

Authors: Craig Campbell https://orcid.org/0000-0001-5216-7564 [email protected], Richard J Barohn, Enrico Bertini, Brigitte Chabrol, Giacomo Pietro Comi, Basil T Darras, Richard S Finkel, … Show All … , 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, on behalf of the PTC124-GD-007-DMD Study Group, and ACT DMD Study Group the Clinical Evaluator Training GroupsAuthor Info & Affiliations
Volume 9, Number 14
https://doi.org/10.2217/cer-2020-0095
PDFFormats

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.

Supplementary Material

File (suppl_file.docx)

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