Ataluren delays clinically meaningful milestones of decline in 6MWD in patients with nmDMD from Study 041, a phase 3, placebo-controlled trial

Topic:

Clinical Trials

Poster Number: M166

Author(s):

Christian Werner, MD, PTC Therapeutics, Shiwen Wu, The Third Medical Center of PLA General Hospital, Beijing, China, Sheffali Gulati, All India Institute of Medical Sciences, New Delhi, India, Hirofumi Komaki, MD, PhD, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan, Rosa E Escobar-Cedillo, Instituto Nacional de Rehabilitación, Mexico City, Mexico, Anna Kostera-Pruszczyk, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, ERN EURO NMD, Jin-Hong Shin, Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, South Korea, 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: Persistent 10% or 5% worsening and a 30m decline in 6-minute walk distance (6MWD) have been established as clinically meaningful milestones of disease progression in patients with Duchenne muscular dystrophy (DMD).

Objective: To assess the effects of ataluren on persistent 10% or 5% worsening and 30m decline in 6MWD in patients with DMD.

Methods: Study 041 (NCT03179631) is an international, phase 3, randomized, double-blind, placebo-controlled 72-week ataluren trial followed by a 72-week open-label period. Eligible boys with genetically confirmed nonsense mutation DMD (nmDMD), aged ≥5 years and with a 6MWD ≥150m were randomized 1:1 to receive ataluren/placebo. The intention-to-treat population comprised boys who received ≥1 dose of study treatment. Predefined subgroups included patients with baseline 6MWD 300–400m, and patients with baseline 6MWD ≥300m and stand from supine ≥5s (primary analysis subgroup). Decline in 6MWD over 72 weeks was assessed in these populations.

Results: In the intention-to-treat population (ataluren, n=183; placebo, n=176), ataluren significantly reduced the risk of persistent 10% and 5% worsening in 6MWD by 31% (p=0.0078) and 30% (p=0.0082), respectively, and 30m decline by 31% (p=0.0067), compared with placebo. In the 6MWD 300–400m subgroup, ataluren significantly reduced the risk of persistent 10% and 5% worsening in 6MWD by 47% (p=0.0011) and 42% (p=0.0029), respectively, and 30m decline by 47% (p=0.0009), compared with placebo. In the primary analysis subgroup, there was a trend towards reduced risk of 10% persistent worsening in 6MWD for patients treated with ataluren compared with placebo, although this did not reach statistical significance (p=0.0659).

Conclusions: These results indicate that ataluren delays clinically meaningful milestones of nmDMD progression that are predictive of ambulatory decline.