[en] Eteplirsen is FDA-approved for the treatment of Duchenne muscular dystrophy (DMD) in exon 51 skip-amenable patients. Previous studies in boys > 4 years of age indicate eteplirsen is well tolerated and attenuates pulmonary and ambulatory decline compared with matched natural history cohorts. Here the safety, tolerability and pharmacokinetics of eteplirsen in boys aged 6-48 months is evaluated. In this open-label, multicenter, dose-escalation study (NCT03218995), boys with 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 safety (primary) and pharmacokinetics (secondary). All 15 participants completed the study. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths or evidence of kidney toxicity. Most treatment-emergent adverse events were mild; most common were pyrexia, cough, nasopharyngitis, vomiting, and diarrhea. Eteplirsen pharmacokinetics were consistent between both cohorts and with previous clinical experience in boys with DMD > 4 years of age. These data support the safety and tolerability of eteplirsen at the approved 30-mg/kg dose in boys as young as 6 months old.
Disciplines :
Pediatrics
Author, co-author :
Mercuri, E; Pediatric Neurology Unit, Università Cattolica del Sacro Cuore Roma, Rome, Italy, Nemo Clinical Centre, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
Seferian, A M; I-Motion Institute, Hôpital Armand Trousseau, Paris, France
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques
Deconinck, N; Neuromuscular Reference Center, UZ Gent, Ghent, Belgium, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 1020 Brussels, Belgium
Stevenson, H; Sarepta Therapeutics, Inc., Cambridge, MA, USA
Ni, X; Sarepta Therapeutics, Inc., Cambridge, MA, USA
Zhang, W; Sarepta Therapeutics, Inc., Cambridge, MA, USA
East, L; Sarepta Therapeutics, Inc., Cambridge, MA, USA
Yonren, S; Sarepta Therapeutics, Inc., Cambridge, MA, USA
Muntoni, F; Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health, London, UK, National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK. Electronic address: f.muntoni@ucl.ac.uk
4658-102 Study Group
Language :
English
Title :
Safety, tolerability and pharmacokinetics of eteplirsen in young boys aged 6-48 months with Duchenne muscular dystrophy amenable to exon 51 skipping.
Study 4658-102 ( NCT03218995 ) was funded by Sarepta Therapeutics , Inc. Medical writing and editorial support was provided by Katherine Alfond, PharmD, RPh, of Sarepta Therapeutics, Inc., and Paraskevi Briassouli, PhD, of Eloquent Scientific Solutions, and was funded by Sarepta Therapeutics , Inc.
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EXONDYS (eteplirsen) injection, for intravenous use [Prescribing information]. 2020, Sarepta Therapeutics, Inc., Cambridge, MA.
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