Kelly G. Knupp, Ingrid E. Scheffer, An-Sofie Schoonjansf, Joseph Sullivan, Lieven Lagae, St´ephane Auvin, Elizabeth A. Thiele, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Katherine C. Nickels, Ronald Davis, Michael D. Lock, David Dai, Timothy Minh, Rebecca Zhang Roper, Najla Dickson, Mélanie Langlois, Am´elie Lothe, Antonio Gil-Nagel
University of Colorado Anschutz Medical Campus. University of Melbourne and Royal Children’s Hospital. University Hospital Antwerp. Benioff Children’s Hospital and University of California San Francisco. University of Leuven. Hôpital Universitaire Robert Debré, Institut Hospitalo-Universitaire Robert-Debré du Cerveau de l’Enfant and Institut Universitaire de France. Massachusetts General Hospital. Meyer Children’s Hospital IRCCS and University of Florence. University of Glasgow. Necker Enfants Malades Hospital, APHP and Université Paris Cité. University of Queensland, St Lucia and Queensland Children’s Hospital. Mayo Clinic. Neurology and Epilepsy Research Center. Syneos Health. Union Chimique Belge.
United States Australia, Belgium, France, Italy and United Kingdom
Epilepsy and Behavior
Epilepsy Behav 2025;
DOI: 10.1016/j.yebeh.2025.110753
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.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes