Ataluren delays loss of ambulation and decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy


Clinical Trials

Poster Number: 52


Francesco Bibbiani MD, Craig McDonald MD, Francesco Muntoni MD, Mark Rance MD, Joseph McIntosh MD, Joel Jiang PhD, Allan Kristensen PhD, Vinay Penematsa MD, Richard Able PhD, Elizabeth Goodwin PhD, Heather Gordish-Dressman PhD, Lauren Morgenroth MSc, Panayiota Trifillis PhD, Mar Tulinius MD


1. PTC Therapeutics, Inc., 2. University of California Davis, 3. Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK, 4. PTC Therapeutics, 5. PTC Therapeutics, 6. PTC Therapeutics, 7. PTC Therapeutics, 8. PTC Therapeutics, 9. PTC Therapeutics, 10. PTC Therapeutics, 11. Center for Genetic Medicine, Children’s National Health System, 12. Therapeutic Research in Neuromuscular Disorders Solutions, 13. PTC Therapeutics, 14. University of Gothenburg, Sweden

Background: Duchenne muscular dystrophy (DMD) is a fatal rare, X-linked disease characterized by progressive muscle weakness. Approximately 10–15% of DMD cases are caused by a nonsense mutation (nmDMD) in the dystrophin gene, resulting in the absence of functional dystrophin. Ataluren (10, 10, 20 mg/kg [morning, midday, and evening]) targets the underlying cause of nmDMD, enabling the formation of a full-length dystrophin.

Objective: To evaluate whether nmDMD patients receiving ataluren + standard of care (SoC; corticosteroids/palliative therapies) experienced a delay in loss of ambulation (LoA) and a slower decline in pulmonary function compared with a matched cohort of patients receiving SoC in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS; NCT00468832).

Methods: Study 019 was a phase 3, long-term (~4.5 years) safety study that enrolled nmDMD patients from prior ataluren clinical trials (NCT01557400) (N=94). Propensity score matching identified Study 019 and CINRG DNHS patients with comparable indicators of disease severity: age at first symptoms, corticosteroid type (deflazacort or other), and duration of use. Kaplan–Meier analyses estimated the age at LoA and at decline in forced vital capacity (FVC) to <60%- or <50%-predicted or <1 L.

Results: Age at LoA was delayed by ~2.5 years in nmDMD patients receiving ataluren in Study 019 compared with CINRG DNHS patients (median ages: Study 019, 15.5 years; CINRG DNHS, 13.0 years; p=0.0079 [each n=60]). In non-ambulatory patients, ataluren was associated with a delay in decline to predicted FVC <60% by ~2.5 years (median ages: Study 019, 18.1 years; CINRG DNHS, 15.5 years; p=0.0376 [each n=45]) and a trend in delay in decline to predicted FVC <50% by ~1 year.

Conclusions: Ataluren + SoC delays LoA and may delay pulmonary function decline in nmDMD patients compared with DMD patients receiving SoC, although longer follow-up will be required to more fully assess this latter outcome.