Effectiveness of Ataluren in Patients with nmDMD: Confirmatory Evidence from the STRIDE Registry and Confirmation of CINRG DNHS as a Valid Comparator

Topic:

Other

Poster Number: 52 S

Author(s):

Jonathan Blaize, PhD, PTC Therapeutics, Christian Werner, Dr. med., PTC Therapeutics Germany GmbH, Frankfurt, Germany, Eugenio Mercuri, MD, PhD, Department of Pediatric Neurology, Catholic University, Rome, Italy, Filippo Buccella, Parent Project APS Italy, Rome, Italy, Andrés Nascimento, MD, Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu, Barcelona, Spain, Már Tulinius, MD, PhD, Department of Pediatrics, Queen Silvia Children’s Hospital, University of Gothenburg, Sweden, Isabelle Desguerre, MD, PhD, Hôpital Necker – Enfants Malades, Paris, France, Maria Bernadete Dutra de Resende, MD, Department of Neurology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil, Craig McDonald, MD, University of California Davis Health, Heather Gordish-Dressman, PhD, Children's National Health System, Lauren Morgenroth, MS, GCG, TRiNDS, LLC., Shelley Johnson, MBA, PMP, PTC Therapeutics Inc., Warren, NJ, USA, Balaji Anbu, PTC Therapeutics Inc., Warren, NJ, USA, Francesco Muntoni, MD, Dubowitz Neuromuscular Centre, UCL and Great Ormond Street Hospital Trust, London, UK

BACKGROUND: The Strategic Targeting of Registries and International Database of Excellence (STRIDE [NCT02369731]) is an international, observational registry evaluating long-term effectiveness and safety of ataluren in patients with nonsense mutation DMD (nmDMD). As of 31 January 2023, STRIDE patients had a 3.5-year delay in loss of ambulation (LoA) versus a propensity-score-matched general DMD population from the CINRG Duchenne Natural History Study (DNHS) receiving standard of care alone.

OBJECTIVE: To assess the reliability of ataluren effectiveness data in STRIDE nmDMD patients and whether mixed-genotype registries can serve as comparators for single-mutation studies.

METHODS: Age at LoA was compared between (1) French DYS Registry nmDMD patients and the DYS overall DMD population; (2) CINRG DNHS nmDMD patients and CINRG DNHS patients with other DMD mutations. Mean (SD) 48-week changes in 10-meter run/walk and four-stair climb times were compared between pooled placebo-treated nmDMD patients from three randomized-controlled trials (RCTs) and CINRG DNHS patients with all DMD mutations.

RESULTS: Median ages at LoA were (1) 10.6 years (n=43) for DYS nmDMD patients versus 11.1 years (n=504) for the DYS overall population; (2) 11.1 years (n=16) for CINRG DNHS nmDMD patients versus 12.0 years (n=382) for CINRG DNHS patients with other DMD mutations. At 48 weeks, pooled placebo-treated RCT patients showed a mean (SD) change of 1.15 (2.52) seconds in time to run/walk 10 meters (n=261) and 2.11 (4.08) seconds to climb four stairs (n=244), compared to 1.20 (2.62) seconds (n=112) and 2.18 (7.46) seconds (n=106), respectively, in CINRG DNHS patients.

CONCLUSIONS: DMD mutation type did not appear to affect age at LoA. Comparable disease progression was seen across mutation types, supporting the use of pooled DMD populations as valid comparators for nmDMD in STRIDE, thus reinforcing ataluren’s observed 3.5-year delay in loss of ambulation.