2025 American Academy of Neurology Abstract Website

Christian Werner¹, Eugenio Mercuri², Filippo Buccella³, Andrés Nascimento Osorio⁴, Már Tulinius⁵, Isabelle Desguerre⁶, Maria Bernadete Dutra de Resende⁷, Craig McDonald⁸, Heather Gordish-Dressman⁹, Lauren Morgenroth¹⁰, Shelley Johnson¹¹, Alexis Krolick¹¹, Balaji Anbu¹¹, Emelline Liu¹¹, Francesco Muntoni¹²
¹PTC Therapeutics Germany GmbH, ²Department of Pediatric Neurology, Catholic University, ³Parent Project APS Italy, ⁴Unidad de Patología Neuromuscular, Hospital Sant Joan de Déu, Universidad de Barcelona, ⁵Department of Pediatrics, Queen Silvia Children’s Hospital, University of Gothenburg, ⁶Hôpital Necker – Enfants Malades, ⁷Department of Neurology, Faculty of Medicine, University of São Paulo, ⁸University of California Davis School of Medicine, ⁹Center for Genetic Medicine, Children's National Health System and the George Washington, ¹⁰Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS), ¹¹PTC Therapeutics Inc., ¹²University College London Great Ormond Street Institute of Child Health

Objective:

To assess the reliability of ataluren effectiveness data in Strategic Targeting of Registries and International Database of Excellence (STRIDE [NCT02369731]) nonsense mutation DMD (nmDMD) patients and whether mutation type is a source of bias.

Background:

STRIDE is an international, observational registry evaluating long-term effectiveness and safety of ataluren in nmDMD patients. 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 receiving standard of care alone.

Design/Methods:

Age at LoA was compared between (1) French DYS Registry nmDMD patients and the DYS overall DMD population; (2) CINRG nmDMD patients and CINRG patients with other DMD mutations; and (3) 3:1 propensity-score-matched STRIDE and CINRG nmDMD patients. STRIDE patients were also matched to the combined intention-to-treat populations of three ataluren randomized controlled trials (RCTs), and 48-week decline in 6-minute walk distance (6MWD) was compared between STRIDE and RCT ataluren-treated or placebo-treated patients.

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 nmDMD patients versus 12.0 years (n=382) for CINRG patients with other DMD mutations; and (3) 13.4 years (n=48) for STRIDE versus 11.1 years (n=16) for CINRG nmDMD patients, indicating a 2.3-year delay in LoA. Mean (SD) 48-week decline in 6MWD was 25.5 (64.8) meters for STRIDE patients versus 25.7 (59.9) meters for RCT ataluren-treated patients and 35.9 (60.2) meters for placebo-treated RCT patients.

Conclusions:

DMD mutation type did not appear to affect age at LoA. LoA was delayed in STRIDE versus CINRG nmDMD patients, and 48-week change in 6MWD was consistent between ataluren-treated STRIDE and RCT patients. Mutation type is therefore not a source of bias, indicating that STRIDE effectiveness data are reliable.