Ataluren preserves muscle burst activity in nmDMD patients from Study 041, a phase 3, randomized, double-blind, placebo-controlled trial


Clinical Trials

Poster Number: 88


Craig McDonald, MD, University of California Davis Health, Sheffali Gulati, All India Institute of Medical Sciences, New Delhi, India, Hirofumi Komaki, MD, PhD, Translational Medical Center, National Center of Neurology and Psychiatry, Rosa E Escobar-Cedillo, Institudo Nacional de Rehabilitación, Ciudad de Mexico, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, Xinguo Lu, Department of Neurology, Shenzhen Children's Hospital, Shenzhen, China, Jin-Hong Shin, Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University Schoo, Vinay Penematsa, MD, PTC Therapeutics Inc., Connie Chou, PTC Therapeutics Inc., Min Lin, PTC Therapeutics Inc., South Plainfield, NJ, USA, Christian Werner, Dr. med., PTC Therapeutics, Pannie (Panayiota) Trifillis, PhD, PTC Therapeutics, Inc., Greg Gordon, MD, PTC Therapeutics, Paula Williams, PTC Therapeutics Inc., Matthew Klein, MD, PTC Therapeutics Inc., South Plainfield, NJ, USA

Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week ataluren trial in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) followed by a 72-week open-label period. Here, we describe the effects of ataluren on muscle burst activity, as assessed by timed function tests (TFTs).

Boys with nmDMD aged ≥5 years, on corticosteroids, and with a 6-minute walk distance (6MWD) ≥150m were eligible and randomized 1:1 to ataluren:placebo. The intention-to-treat (ITT) population comprised randomized boys who received ≥1 dose of study treatment; a key subgroup included boys with 300–400m 6MWD. Change from baseline to week 72 in TFT (10-metre walk/run, 4-stair ascent, 4-stair descent) results were secondary endpoints.

The ITT population comprised a total of 359 patients with nmDMD randomized to receive ataluren (n=183) or placebo (n=176); groups were balanced according to enrollment age, baseline 6MWD, corticosteroid use and supine-to-stand time. Treatment with ataluren significantly reduced the mean change from baseline in time to perform the 10-metre walk/run vs placebo in the ITT population by 20% (−0.78s, p=0.0422) and the 300–400m 6MWD subgroup by 30% (−1.29s, p=0.0429). Significant differences in the mean change from baseline in time to perform the 4-stair ascent favored ataluren in the ITT population (−1.06s, p=0.0293) and 300–400m 6MWD subgroup (−2.29s, p=0.0050), representing a relative change vs placebo of 18% and 30%, respectively. The mean change from baseline in time to perform the 4-stair descent was numerically reduced in patients who received ataluren vs placebo (ITT population: −0.29s, p=0.5749; 300–400m 6MWD subgroup: −0.97s, p=0.2714).

These results from Study 041 demonstrate that ataluren preserves performance in TFTs, and therefore muscle burst activity, in patients with nmDMD.