Ataluren Preserves Upper Limb Function in nmDMD Patients From Study 041, a Phase 3 Placebo-Controlled Trial, and the STRIDE Registry


Clinical Trials

Poster Number: 115


Christian Werner, Dr. med., PTC Therapeutics, Craig McDonald, MD, University of California Davis Health, Eugenio Mercuri, MD, PhD, Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Francesco Muntoni, MD, UCL Institute of Child Health and Great Ormond Street Hospital for Children, Heather Gordish-Dressman, PhD, Children’s National Hospital, Lauren Morgenroth, MS, CGC, TRiNDS, Maria Bernadete Dutra Resende, Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, Shuizhen Zhou, Department of Neurology, Children's Hospital of Fudan University & National Children Medical Center, Mathukumalli Lakshmi Neeharika, Nizam’s Institute of Medical Sciences, Kazuhiro Haginoya, Department of Pediatric Neurology, Miyagi Children's Hospital, Leigh Maria Ramos-Platt, MD, Children's Hospital Los Angeles/USC, Paula Williams, PTC Therapeutics Inc., Vinay Penematsa, MD, PTC Therapeutics Inc., Connie Chou, PTC Therapeutics Inc., Shelley Johnson, DBA, MBA, PTC Therapeutics Inc, Karyn Koladicz, MD, PTC Therapeutics, Nicholas Mastrandrea, PhD, PTC Therapeutics, Pannie (Panayiota) Trifillis, PhD, PTC Therapeutics, Inc.

Background: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by a lack of functional dystrophin. Ataluren promotes readthrough of an in-frame premature stop codon to produce full-length dystrophin and is indicated for the treatment of patients with nonsense mutation (nm) DMD. Study 041 (NCT03179631) is a phase 3, double-blind, placebo-controlled 72-week trial. The STRIDE Registry (NCT02369731) is an ongoing, long-term, real-world evidence study.

Objectives: To assess performance of upper limb (PUL) function in patients with nmDMD receiving ataluren plus standard of care (SoC) in Study 041 and in the STRIDE Registry.

Methods: In Study 041, boys with nmDMD aged ≥5 years, on a stable corticosteroid regimen, and with a 6-minute walk distance (6MWD) ≥150m were randomized 1:1, ataluren:placebo. The intention-to-treat (ITT) population comprised randomized boys who received at least one dose of study treatment (N=359; mean age 8.1 years); a key subgroup included those with baseline 300–400m 6MWD (n=169). STRIDE patients were propensity-score matched to patients receiving SoC alone in CINRG DNHS (NCT00468832), yielding a comparable population (N=261). Kaplan-Meier analyses estimated age at loss of upper limb function.

Results: Least-squares mean PUL total score change from baseline to week 72 (by MMRM analysis) numerically favored ataluren versus placebo (0.44, p=0.1059) in the Study 041 ITT population and was significant in the 300–400m 6MWD subgroup (1.02, p=0.0165).

In matched STRIDE versus CINRG patients (mean last assessment age, 13.1 versus 14.6), ataluren preserved hand-to-mouth function by 3.4 years (p=0.0046) assessed by entry level items of PUL versus Brooke Scale, respectively. Median age at loss of overhead reach favored STRIDE, consistent with the overall trend (15.8 versus 12.6; p=0.2872). Median age at loss of distal hand function was non-estimable for STRIDE patients.

Conclusions: These results indicate that ataluren may preserve upper limb function in patients with advanced nmDMD.