Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/31005
Title: Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: interim analysis of an open-label extension study.
Austin Authors: Knupp, Kelly G;Scheffer, Ingrid E ;Ceulemans, Berten;Sullivan, Joseph;Nickels, Katherine C;Lagae, Lieven;Guerrini, Renzo;Zuberi, Sameer M;Nabbout, Rima;Riney, Kate;Agarwal, Anupam;Lock, Michael;Dai, David;Farfel, Gail M;Galer, Bradley S;Gammaitoni, Arnold R;Polega, Shikha;Davis, Ronald;Gil-Nagel, Antonio
Affiliation: University of Colorado, Children's Hospital Colorado, Aurora, CO, USA.
School of Clinical Medicine, University of Queensland, St Lucia, QLD, Australia
Neuroscience Unit, Queensland Children's Hospital, South Brisbane, QLD, Australia
Austin Health
Department of Paediatric Neurology, Antwerp University Hospital, Antwerp, Belgium.
University of California San Francisco Weill Institute for Neurosciences, Benioff Children's Hospital, San Francisco, CA, USA..
Mayo Clinic, Department of Neurology, Rochester, MN, USA.
Member of the European Reference Network EpiCARE; Department of Paediatric Neurology, University of Leuven, Leuven, Belgium..
Pediatric Neurology and Neurogenetics Unit, Anna Meyer Children's Hospital, University of Florence, Florence, Italy; IRCCS Fondazione Stella Maris, Pisa, Italy..
Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, United Kingdom..
Reference Centre for Rare Epilepsies, Hôpital Universitaire Necker-Enfants Malades, APHP, Member of EPICARE, Institut Imagine, Université Paris Cité, Paris, France..
Formerly Zogenix, Inc. (now a part of UCB), Emeryville, CA, USA..
Independent consultant, Zogenix, Inc. (now a part of UCB); Haiku, HI, USA..
Syneos Health, Morrisville, NC, USA..
Formerly Zogenix, Inc. (now a part of UCB), Emeryville, CA, USA..
Zogenix, Inc. (now a part of UCB), Emeryville, CA, USA..
Neurology and Epilepsy Research Center, Orlando, FL, USA..
Hospital Ruber Internacional, Madrid, Spain..
Issue Date: 2023
Date: 2022
Publication information: Epilepsia 2023; 64(1)
Abstract: To evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). 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 0.2 mg/kg/day fenfluramine and, after 1 month, were titrated to 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. As of 10/19/2020, 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<0.0001); 75/241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in non-drop seizure frequency was -45.9% (n=192; P=0.0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (P<0.0001; n=106) and 35.8% (P<0.0001; n=186), respectively. A total of 37.6% (95% 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 (CGI-I) 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. 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 SUDEP. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.
URI: https://ahro.austin.org.au/austinjspui/handle/1/31005
DOI: 10.1111/epi.17431
ORCID: https://orcid.org/0000-0002-1967-0827
https://orcid.org/0000-0002-2311-2174
https://orcid.org/0000-0002-6579-3035
https://orcid.org/0000-0002-7118-0139
https://orcid.org/0000-0002-7272-7079
https://orcid.org/0000-0001-5877-4074
https://orcid.org/0000-0002-1122-3555
https://orcid.org/0000-0002-4735-3327
https://orcid.org/0000-0002-4775-2862
Journal: Epilepsia
PubMed URL: 36196777
Type: Journal Article
Subjects: Lennox-Gastaut syndrome
developmental and epileptic encephalopathies
fenfluramine
long-term open-label extension
Appears in Collections:Journal articles

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