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.
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 / Knupp, Kelly G; Scheffer, Ingrid E; Schoonjans, An-Sofie; Sullivan, Joseph; Lagae, Lieven; Auvin, Stéphane; Thiele, Elizabeth A; Guerrini, Renzo; Zuberi, Sameer M; Nabbout, Rima; Riney, Kate; Nickels, Katherine C; Davis, Ronald; Lock, Michael D; Dai, David; Minh, Timothy; Zhang Roper, Rebecca; Dickson, Najla; Langlois, Mélanie; Lothe, Amélie; Gil-Nagel, Antonio. - In: EPILEPSY & BEHAVIOR. - ISSN 1525-5069. - ELETTRONICO. - 173:(2025), pp. 110753.0-110753.0. [10.1016/j.yebeh.2025.110753]
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
Guerrini, Renzo;
2025
Abstract
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.
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