Ataluren slows the decline of muscle function in patients with nmDMD: a meta-analysis of three randomized, double-blind, placebo-controlled trials


Clinical Trials

Poster Number: M167


Christian Werner, MD, PTC Therapeutics, Yuh-Jyh Jong, MD, DMSci, Graduate Institute of Clin Med, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Peter Karachunski, University of Minnesota, Minneapolis, MN, USA, Jeffrey Statland, MD, University of Kansas Medical Center, Richard Roxburgh, Neurogenetics Clinic Centre for Brain Research, University of Auckland, Auckland, NZ, Anita Cairns, Neurosciences Department, Queensland Children’s Hospital, South Brisbane, QLD, Australia, Yasuhiro Takeshima, Department of Paediatrics, Hyogo Medical University, Nishinomiya, Japan, Kazuhiro Haginoya, Department of Pediatric Neurology, Miyagi Children's Hospital, Sendai, Japan, Vinay Penematsa, MD, PTC Therapeutics Inc., South Plainfield, NJ, USA, Connie Chou, PTC Therapeutics Inc., South Plainfield, NJ, USA, Jonathan Blaize, PhD, PTC Therapeutics, South Plainfield, NJ, USA, Bethany Freel, PhD, PTC Therapeutics, South Plainfield, NJ, USA, Paula Williams, PTC Therapeutics Inc., South Plainfield, NJ, USA

Background: Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week trial of ataluren in patients with nonsense mutation DMD (nmDMD) followed by a 72-week open-label period.

Objective: To assess ataluren muscle function efficacy results from a meta-analysis of the Study 041 placebo-controlled phase and two randomized, double-blind, placebo-controlled, 48-week ataluren trials (Study 007 [phase 2b; NCT00592553] and ACT DMD [phase 3; NCT01826487]).

Methods: In all three studies, boys were eligible if they had genetically confirmed nmDMD. The meta-analysis used a weighted random-effects model and included intention-to-treat populations from Study 041, Study 007 and ACT DMD. Endpoints included changes from baseline to week 48 in 6MWD, TFTs and NSAA total and linear scores (Study 041 and ACT DMD only); mean 48-week change in 6MWD was assessed in a subgroup of patients with baseline 6MWD 300–400m.

Results: The meta-analysis included 354 ataluren-treated patients and 347 placebo-treated patients. The differences in change from baseline to week 48 in 6MWD, TFTs and the NSAA scores between ataluren- and placebo-treated patients were statistically significant, favoring ataluren (least-squares mean difference; 6MWD: 15.8m, p=0.0032; 10m walk/run: −1.1s, p=0.0026; climb four stairs: −1.3s, p=0.0025; descend four stairs: −1.3s, p=0.0021; NSAA total score: 1.1, p=0.0010; NSAA linear score: 2.6, p=0.0036). In the 6MWD 300–400m subgroup, ataluren significantly slowed 6MWD decline by 33.7m versus placebo (p<0.0001). Conclusion: In this meta-analysis of a large, heterogeneous population from the intention-to-treat populations of Study 041, Study 007 and ACT DMD, ataluren slowed decline in muscle function across multiple clinically meaningful endpoints versus placebo.