Safety and Tolerability of Eteplirsen in Patients 6–48 Months Old With DMD Amenable to Exon 51 Skipping: An Open-Label Extension Study


Clinical Trials

Poster Number: M173


Ihor Sehinovych, PharmD, Sarepta Therapeutics, Inc., Eugenio Mercuri, MD, PhD, Pediatric Neurology Unit, Università Cattolica del Sacro Cuore Roma, Rome, Italy;, Andreea M. Seferian, MD, Assistance Publique Hôpitaux de Paris, Sorbonne Université, Institut de Myologie, Nicolas Deconinck, MD, PhD, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des, Larry Orogun, MD, MSc, Sarepta Therapeutics, Xiao Ni, PhD, Sarepta Therapeutics, Inc., Wenfei Zhang, PhD, Sarepta Therapeutics, Inc., Kerri Drummond, BS, Sarepta Therapeutics, Inc., Francesco Muntoni, FRCPCH, FMedSci, University College London, National Institute for Health Research Great Ormond Street Hospital

Eteplirsen is indicated for treatment of exon 51 skip-amenable patients with Duchenne muscular dystrophy (DMD). Study 4658-102 (NCT03218995), a phase 2, open-label, dose-escalation trial, showed that eteplirsen (30 mg/kg IV once weekly) was well tolerated in patients aged 24 to 48 months (cohort 1, n=9) and 6 to <24 months (cohort 2, n=6) up to 96 weeks. Results from the open-label extension (OLE), which assessed the ongoing safety and tolerability in patients who were treated for up to ~5 years (258 weeks) are reported. Safety endpoints included incidence and frequency of treatment-emergent adverse events (TEAEs) and clinically significant laboratory abnormalities. Fourteen (93.3%) of 15 patients were enrolled in the OLE when the study was terminated by the sponsor to reduce trial burden (ensuring continued treatment if desired). At OLE baseline, 4/15 (26.7%, cohort 1) were receiving corticosteroids with 11 patients receiving corticosteroids during the OLE. From the start of the OLE, patients received a mean (SD) of 108.5 (37.1) eteplirsen infusions and were on eteplirsen for a mean (SD) of 120.1 (35.79) weeks. All patients experienced ≥1 TEAE; most were mild, consistent with those commonly seen in pediatric populations (cough, pyrexia, rhinorrhea, nasopharyngitis), and reduced in frequency and severity compared with TEAEs in the parent study. Three patients experienced mild treatment-related TEAEs (catheter-site swelling, chromaturia, abnormal urine albumin/creatinine ratio); there were no port-related infections. One serious TEAE was reported (influenza; unrelated to treatment). Eteplirsen was well tolerated, with no treatment-related discontinuations, deaths, or evidence of kidney toxicity. The safety profile of eteplirsen in the OLE was consistent with the known safety profile, with no new safety signals up to 162 weeks of treatment and no discernible difference between cohort 1 and 2. These data support the safety and tolerability of eteplirsen in patients as young as 6 months old.