{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:11:10Z","timestamp":1791396670081,"version":"4.3.3"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012739","name":"Zogenix","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was undertaken to evaluate the long\u2010term safety and effectiveness of fenfluramine in patients with Lennox\u2013Gastaut syndrome (LGS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible patients with LGS who completed a 14\u2010week phase 3 randomized clinical trial enrolled in an open\u2010label extension (OLE; NCT03355209). All patients were initially started on .2\u00a0mg\/kg\/day fenfluramine and after 1\u00a0month were titrated by effectiveness and tolerability, which were assessed at 3\u2010month intervals. The protocol\u2010specified treatment duration was 12\u2009months, but COVID\u201019\u2010related delays resulted in 142 patients completing their final visit after 12\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3\u2009\u00b1\u20097.6\u2009years (79 [32%] adults) and median fenfluramine treatment duration was 364\u2009days; 88.3% of patients received 2\u20134 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was \u221228.6% over the entire OLE (<jats:italic>n<\/jats:italic>\u00a0=\u00a0241) and \u221250.5% at Month 15 (<jats:italic>n<\/jats:italic>\u00a0=\u00a0142,<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001); 75 of 241 patients (31.1%) experienced \u226550% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was \u221245.9% (<jats:italic>n<\/jats:italic>\u00a0=\u00a0192,<jats:italic>p<\/jats:italic>\u00a0=\u00a0.0038). Generalized tonic\u2013clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001,<jats:italic>n<\/jats:italic>\u00a0=\u00a0106) and 35.8% (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001,<jats:italic>n<\/jats:italic>\u00a0=\u00a0186), respectively. A total of 37.6% (95% confidence interval [CI]\u00a0=\u00a031.4%\u201344.1%,<jats:italic>n<\/jats:italic>\u00a0=\u00a0237) of investigators and 35.2% of caregivers (95% CI\u00a0=\u00a029.1%\u201341.8%,<jats:italic>n<\/jats:italic>\u00a0=\u00a0230) rated patients as Much Improved\/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment\u2010emergent 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>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\u2010term. Fenfluramine may provide an important long\u2010term treatment option for LGS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17431","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T09:40:08Z","timestamp":1664962808000},"page":"139-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox\u2013Gastaut syndrome: Interim analysis of an open\u2010label extension study"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-0827","authenticated-orcid":false,"given":"Kelly G.","family":"Knupp","sequence":"first","affiliation":[{"name":"University of Colorado, Children's Hospital Colorado Aurora Colorado 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