2024 American Academy of Neurology Abstract Website

Yuh-Jyh Jong¹, Peter Karachunski², Jeffrey Statland³, Michelle Lorentzos⁴, Anita Cairns⁵, Yasuhiro Takeshima⁶, Kazuhiro Haginoya⁷, Vinay Penematsa⁸, Connie Chou⁸, Paula Williams⁹, Christian Werner⁸
¹Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, ²University of Minnesota, ³University of Kansas Medical Center, ⁴The Children's Hospital at Westmead, ⁵Neuroscience, Queensland Chlidren's Hospital, ⁶Pediatrics, Hyogo Medical University, ⁷Miyagi Children'S Hospital, ⁸PTC Therapeutics, Inc, ⁹PTC Therapeutics, Inc.

Objective:

To report 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]).

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.

Design/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).

Conclusions:

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.