Demographics and safety data from patients with nonsense mutation Duchenne muscular dystrophy receiving ataluren in the STRIDE Registry


Topic:

Real World Data - Disease registries, natural history, post marketing surveillance

Poster Number: 46

Author(s):

Francesco Muntoni, Filippo Buccella, Isabelle Desguerre, Janbernd Kirschner, Andrés Nascimento Osorio, MD, PhD, Már Tulinius, Joel Jiang, Allan Kristensen, Panayiota Trifillis, PhD, Claudio L Santos

Institutions:

1. Dubowitz Neuromuscular Centre & MRC Centre for Neuromuscular Diseases, University College London, 2. Parent Project Italy APS, 3. APHP Necker – Enfants Malades Hospital, Paris V Descartes University, 4. Medical Center – University of Freiburg, 5. Hospital Sant Joan de Déu Unidad de Patología Neuromuscular, Universidad de Barcelona, 6. Department of Pediatrics, Gothenburg University, 7. PTC Therapeutics Inc, 8. PTC Therapeutics Inc, 9. PTC Therapeutics Inc, 10. 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. Strategic Targeting of Registries and International Database of Excellence (STRIDE; NCT02369731) is an ongoing registry providing real-world data on ataluren use in patients with nmDMD.

OBJECTIVES
To describe the demographics of the STRIDE population and the interim safety results as of the latest data cut-off date of 31 January 2019.

APPROACH
Data from enrolled patients are collected at the consent date; for patients who initiated ataluren as part of a commercial or early access program before enrollment, data for the period prior to enrollment are obtained retrospectively. Patients will be followed up for ≥5 years or until study withdrawal.

RESULTS
As of 31 January 2019, 220 boys had been enrolled in STRIDE in 11 countries and received at least one ataluren dose. Total mean (standard deviation [SD]) exposure to ataluren was 822 (368) days, equivalent to 495 patient-years. Safety outcomes were consistent with the known safety profile of ataluren. Fourteen boys discontinued the study. Of 220 boys enrolled, 210 had genetically confirmed nmDMD; 10 patients with frameshift mutations were excluded. Most patients were Caucasian (140/210 [66.7%]) and the mean (SD) age at consent date was 10.6 (3.6) years (n=210). Mean (SD) age at first symptoms was 2.8 (1.8) years (n=193); at nmDMD confirmation it was 5.2 (2.9) years (n=200). Median time between first symptoms and confirmation was 1.6 years (n=186). Most patients used concomitant corticosteroids (191/220 [86.8%]).

CONCLUSIONS
STRIDE constitutes the first drug registry for patients with nmDMD. Analyses of effectiveness data from STRIDE patients will provide insights into the real-world long-term effectiveness and safety of ataluren.