Adulthood Milestones in Duchenne & Becker Muscular Dystrophy


Clinical Trials

Poster Number: 112


Eugenio Mercuri, Andreea M Seferian, Laurent Servais, I-Motion Institute, Hôpital Armand Trousseau, Nicolas Deconinck, MD, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des E, Herb Stevenson, Sarepta Therapeutics, Inc, Lily East, Sarepta Therapeutics, Inc, Wenfei Zhang, Sarepta Therapeutics, Inc, Sameer Upadhyay, Sarepta Therapeutics, Inc, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, London, UK

Background: Eteplirsen is indicated for treatment of exon 51 skip-amenable patients with Duchenne muscular dystrophy (DMD). Previous studies in patients >4 years of age indicate eteplirsen is well tolerated and attenuates pulmonary and ambulatory declines compared with matched natural history cohorts. Objective: Here we evaluate the safety, tolerability, and pharmacokinetics of eteplirsen in patients aged 6–48 months, the youngest population of patients with DMD in a clinical trial to date, in Study 4658-102 (NCT03218995). Methods: In this open-label, multicenter, dose-escalation study, patients who had a confirmed mutation of the DMD gene amenable to exon 51 skipping (Cohort 1: aged 24–48 months, n=9; Cohort 2: aged 6 to <24 months, n=6) received ascending doses (2, 4, 10, 20, 30 mg/kg) of once-weekly eteplirsen intravenously over 10 weeks, continuing at 30 mg/kg up to 96 weeks. Endpoints included incidence of adverse events and clinically significant laboratory abnormalities (primary) and pharmacokinetics (secondary). Results: All patients completed the study (N=15). Average time since diagnosis was 10.5 months, and most (13/15, 86.7%) were not taking corticosteroids. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths, or evidence of kidney toxicity. Most treatment-emergent adverse events were mild, and the most common were consistent with those commonly seen in pediatric populations (pyrexia, nasopharyngitis, vomiting, cough, diarrhea). Eteplirsen pharmacokinetics were consistent between both cohorts and aligned with expectations based on previous clinical experience in boys with DMD older than 4 years of age. Conclusion: These safety and pharmacokinetic results contribute to the body of evidence supporting the early use of eteplirsen in boys with DMD.