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

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 investigators rated 59.9 % and 57.0 % of patients as improved, respectively. At Month 12, mean overall patient quality of life and caregiver anxiety on HADS significantly improved from baseline. SIGNIFICANCE: These results support the long-term safety and effectiveness of fenfluramine in patients with LGS, with no new safety signals identified, and sustained reductions in seizures and improvement in global functioning observed.