Abstract Details

Title Interim Analysis of Long-Term Safety and Efficacy of FINTEPLA (fenfluramine) in Patients with Lennox-Gastaut Syndrome

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S13 - Epilepsy/Clinical Neurophysiology (EEG): Antiseizure Medications (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Background LGS is a treatment-resistant developmental and epileptic encephalopathy (DEE) with multiple seizure types and high rates of morbidity and mortality. During the randomized controlled trial, patients with LGS treated with fenfluramine 0.7 mg/kg/day demonstrated a 26.5% median reduction in seizures associated with a drop vs 7.6% in the placebo group, with an estimated median difference of -19.9% (P=0.0013).

Objective To evaluate the long-term safety and efficacy of fenfluramine in patients with Lennox-Gastaut syndrome (LGS).

Design/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 0.2 mg/kg/day fenfluramine and were titrated to effectiveness/tolerability after 1 month. Effectiveness/tolerability were assessed at 3-month intervals.

Results 247 patients were enrolled in the OLE as of the data cut-off for this interim analysis (10/19/2020). Mean age was 14.3±7.6 years (79 [32%] adults, ≥18 years). The 5 most common concomitant antiseizure medications (ASM) were valproate, clobazam, lamotrigine, levetiracetam, and rufinamide; 88.3% of patients received 2-4 concomitant ASMs. Median percentage decrease in monthly frequency of seizures resulting in drops (hereafter “drop seizure frequency”) at Month 3 was -39.4% and was sustained up to 12 months (-51.8%) By the end of Months 10-12 in the OLE period, 87 patients (51.2%) experienced ≥50% reduction in drop seizure frequency, and approximately 50% of investigators and caregivers rated patients as “Much Improved”/“Very Much Improved”. The 2 most frequent treatment-emergent adverse events during the entire OLE period were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed.

Conclusions Patients with LGS experienced sustained (39.4%-51.8% ) reduction in drop seizure frequency during fenfluramine treatment from 3-12 months. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important new treatment option for LGS.

Authors/Disclosures
Kelly G. Knupp, MD (Children's Hospital Colorado) PRESENTER	Dr. Knupp has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for zogenix. Dr. Knupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for encoded. Dr. Knupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for stoke. The institution of Dr. Knupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW pharmaceuticals. Dr. Knupp has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsy Research.
Ingrid E. Scheffer, MBBS, PhD, FRACP, AO (Melbourne Brain Centre)	Dr. Scheffer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven Pharmaceuticals, Inc. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerecin Inc. The institution of Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epilepsy Consortium. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Longboard Pharmaceuticals . Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bellberry Ltd. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Medical Research Future Fund, Australia. The institution of Dr. Scheffer has received research support from Shenzhen Sanming Development Grant . The institution of Dr. Scheffer has received research support from Einstein Visiting Fellowship. Dr. Scheffer has received intellectual property interests from a discovery or technology relating to health care. Dr. Scheffer has received intellectual property interests from a discovery or technology relating to health care. Dr. Scheffer has received intellectual property interests from a discovery or technology relating to health care. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Akumentis. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with Biocodex. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with BioMarin. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Chiesi. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with Eisai. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference with Encoded Therapeutics. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Liva Nova. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Nutricia. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with Stoke Therapeutics. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Travel/Conference/Speaker honoraria with UCB. Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Speaker honoraria with Zuellig Pharma Inc.. Dr. Scheffer has a non-compensated relationship as a Trial Investigator with Anavex Life Sciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Cerebral Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Cerecin that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Cereval Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Eisai that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Scientific Advisory Board, Trial investigator with Encoded Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with EpiMinder Inc that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with ES-Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Knopp Biosciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Marinus Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Neurocrine BioSciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Ovid Therapeutics that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with SK Life Science that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator, Scientific Advisory Board with Takeda Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Xenon Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Zogenix that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Neurology that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Epilepsy Currents that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Epileptic Disorders that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with The Lancet Neurology that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Journal Editorial Board with Progress in Epileptic Disorders series that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Director with Australian Academy of Health and Medical Sciences that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Director with Royal Society (Australia). that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
Katherine C. Nickels, MD, FAAN (Mayo Clinic)	The institution of Dr. Nickels has received research support from Zogenix. The institution of Dr. Nickels has received research support from Marinus. The institution of Dr. Nickels has received research support from Bio-Pharm Solutions. The institution of Dr. Nickels has received research support from Pediatric Epilepsy Research Foundation. Dr. Nickels has received personal compensation in the range of $500-$4,999 for serving as a Faculty with J. Kiffin Penry Educational Programs.
Lieven G. Lagae, PhD (University Hospital Gasthuisberg)	Dr. Lagae has nothing to disclose.
Renzo Guerrini (Hotelplan)	Renzo Guerrini has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Anupam Agarwal, MD (Zogenix)	Dr. Agarwal has received personal compensation for serving as an employee of ZOGENIX.
	No disclosure on file
Gail M. Farfel, PhD	Dr. Farfel has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Durect Corp. Dr. Farfel has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Zogenix. Dr. Farfel has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for AvroBio. Dr. Farfel has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Arnold Gammaitoni, PharmD (Zogenix)	Dr. Gammaitoni has received personal compensation for serving as an employee of Zogenix Inc.. Dr. Gammaitoni has received stock or an ownership interest from Zogenix Inc..
	No disclosure on file
Antonio Gil-Nagel, MD (Hospital Ruber Internacional)	Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI . Dr. Gil-Nagel has received personal compensation in the range of $0-$499 for serving as a Consultant for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Angelini Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoke . Dr. Gil-Nagel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zogenix . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Angelini Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIAL . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EISAI . Dr. Gil-Nagel has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for GW Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PTC Therapeutics . Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Gil-Nagel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zogenix . The institution of Dr. Gil-Nagel has received research support from Jazz Pharmaceuticals. The institution of Dr. Gil-Nagel has received research support from PTC Therapeutics. The institution of Dr. Gil-Nagel has received research support from Zogenix. The institution of Dr. Gil-Nagel has received research support from Agencia Estatal Innovacion.