Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open‐label extension study
Year: 2022
Type: article
Abstract: OBJECTIVE: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). METHODS: Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months. RESULTS: As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2-4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was -28.6% over the entire OLE (n = 241) and -50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was -45.9% (n = 192, p = .0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%-44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%-41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. SIGNIFICANCE: Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.
Source: Epilepsia
DOI: 10.1111/epi.17431
Authors: Kelly G. Knupp, Ingrid E. Scheffer, Berten Ceulemans, Joseph Sullivan, Katherine C. Nickels, Lieven Lagae, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Anupam Agarwal, Michael Lock, David Dai, Gail M. Farfel, Bradley S. Galer, Arnold R. Gammaitoni, Shikha Polega, Ronald Davis, Antonio Gil‐Nagel
Institutions: Children's Hospital Colorado, Royal Children's Hospital, The University of Melbourne, Austin Hospital, Antwerp University Hospital, University of California, San Francisco, Mayo Clinic, KU Leuven, Meyer Children's Hospital, Fondazione Stella Maris, University of Florence, Royal Hospital for Children, Hôpital Necker-Enfants Malades, Université Paris Cité, Institut des Maladies Génétiques Imagine, The University of Queensland, Children's Health Queensland Hospital and Health Service, Zogenix (United States), Syneos Health (United States), Hospital Ruber Internacional
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,950
Funders: GlaxoSmithKline, Pediatric Epilepsy Research Foundation, Dravet Syndrome UK, Zogenix, Ultragenyx Pharmaceutical, GW Pharmaceuticals, Zynerba Pharmaceuticals, Epilepsy Research UK, Eisai, Epilepsiatutkimussäätiö, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Health Research Council of New Zealand
OpenAlex ID: W4301594771