Final analysis from an open-label extension study of fenfluramine for the treatment of seizures in Lennox-Gastaut syndrome: long-term impact on patients and caregivers

作者：Kelly G. Knupp, Ingrid E. Scheffer, An‐Sofie Schoonjans, Joseph Sullivan, Lieven Lagae, Stéphane Auvin, Elizabeth A. Thiele, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Katherine Nickels, Ronald L. Davis, Michael Lock, David Dai, Timothy Minh, Robyn Roper, Najla Dickson, Mélanie Langlois, Amélie Lothe, António Gil‐Nagel · 发表于：Epilepsy & Behavior · 年份：2025 · DOI：10.1016/j.yebeh.2025.110753 · 被引用次数：7 · 研究领域：Epilepsy research and treatment、Neuroscience and Neuropharmacology Research、Neonatal and fetal brain pathology

OBJECTIVE: To describe long-term safety and effectiveness of fenfluramine in pediatric and adult patients with Lennox-Gastaut syndrome (LGS) from the final analysis of an open-label extension (OLE) study. METHODS: Patients (aged 2-35y) who participated in the randomized controlled trial (RCT) were eligible to continue in this OLE (NCT03355209). Fenfluramine 0.2 mg/kg/day was initiated; after one month, titration up to 0.7 mg/kg/day (26 mg/day maximum) was allowed. Key endpoints: incidence of treatment-emergent adverse events (TEAEs), median percentage change from RCT baseline in frequency of seizures associated with a fall, improvement by caregivers and investigators on Clinical Global Impression-Improvement (CGI-I), change from baseline in Quality of Life in Childhood Epilepsy Questionnaire scores, and Hospital Anxiety and Depression Scale (HADS) in parents/caregivers. RESULTS: 247 patients enrolled: 158 (64.0 %) patients completed this OLE. Mean ± SD age, 14.3 ± 7.6y; median fenfluramine exposure, 364d (range, 19-537); mean ± SD fenfluramine daily dose, 0.4 ± 0.1 mg/kg/day. TEAEs in ≥10 % of patients: decreased appetite, fatigue, nasopharyngitis, seizure, pyrexia; no valvular heart disease or pulmonary arterial hypertension cases. Median change in frequency of seizures associated with a fall from Month 2 to end of study: -31.1 % (n = 240; P < 0.0001); pediatric: -27.6 % (n = 170; P = 0.0005), adult: -40.0 % (n = 70; P < 0.0001). On last-visit CGI-I, caregivers and investiga...