Abstract Details

Title Impact of Fenfluramine on Drop Seizure Frequency in Adults or Dose-Capped Patients With Lennox-Gastaut Syndrome: Comparative Analysis of Clinical Trial Data

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S44 - Epilepsy/Clinical Neurophysiology (EEG): Epilepsy Outcomes (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Background Treatment for LGS is individualized and may evolve as the syndrome persists and changes into adulthood. Patients weighing ≥37.5kg (ie, most adults) had their doses capped at 26 mg/day and therefore received doses ≤0.7mg/kg/day.

Objective To evaluate fenfluramine treatment on drop seizure frequency (DSF) in adults and patients who were dose-capped at 26mg/day in a randomized clinical trial (RCT) or open-label extension (OLE) for Lennox-Gastaut syndrome (LGS).

Design/Methods After 4-weeks’ baseline in the RCT, LGS patients (2-35 years) were randomized to fenfluramine 0.7mg/kg/day (maximum, 26mg/day), fenfluramine 0.2mg/kg/day, or placebo for 2 weeks (titration) and 12 additional weeks. Eligible patients continuing into the OLE started on fenfluramine at 0.2mg/kg/day after a blinded 2-week taper. After 1 month, doses were titrated to effect/tolerability.

Results In the RCT, 76 adults (≥18-35 years) and 187 children/adolescents (2-17 years) were randomized to fenfluramine 0.7mg/kg/day (n=25 and 62, respectively), fenfluramine 0.2mg/kg/day (n=25 and 64), or placebo (n=26 and 61). Among both adults and children/adolescents, median DSF reduction from baseline was numerically greater in the 0.7mg/kg/day fenfluramine group (36.3%; P=0.0877 vs placebo [17.8%] and 20.3%; P=0.0106 vs placebo [4.8%]; nonparametric ANCOVA) and the 0.2mg/kg/day fenfluramine group (33.1%; P=0.1777 vs placebo [17.8%] and 7.2%; P=0.3268 vs placebo [4.8%]). Forty-seven patients weighed ≥37.5kg and were dose-capped at 26mg/day; median percentage reduction from baseline in DSF was greater than placebo (n=45) (35.3% vs 11.2%; P=0.0079 [ANCOVA]). In the OLE, 75% received ≤0.5mg/kg/day fenfluramine. Median reduction in DSF from baseline was 39.0% in adults (n=70) (P<0.0001, Wilcoxon signed rank test) and 25.6% in children/adolescents (n=171) (P=0.0037). Median percentage reductions in DSF were similar in patients weighing <37.5kg (28.3%; P=0.0127 [Wilcoxon signed rank test]) and ≥37.5kg (29.0%; P<0.0001).

Conclusions These data suggest that fenfluramine treatment results in effective, sustained DSF reduction in adults with LGS and patients weighing ≥37.5kg and dose-capped at 26mg/day.

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
Shikha Polega (UCB)	Shikha Polega has received personal compensation for serving as an employee of UCB. Shikha Polega has stock in UCB. Shikha Polega has stock in Zogenix.
	No disclosure on file
	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.