Abstract Details

Title Fenfluramine Treatment Is Associated With Improvement in Everyday Executive Function in Adults With Lennox-Gastaut Syndrome: Post-Hoc Analysis of Dose Effects From a Phase 3 Trial Rationale

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-001

Objective Examine the associations between placebo and fenfluramine (FFA) treatment groups and the likelihood of clinically meaningful change on everyday executive function (EF) in adults with Lennox-Gastaut syndrome (LGS) over a 14-week phase 3 trial.

Background LGS patients have problems with everyday EF. Children and adolescents with LGS showed improvement in everyday EF following FFA treatment. We evaluated whether caregiver-rated everyday EF improved after FFA treatment in adults with LGS.

Design/Methods

Data were analyzed for 57 adults with LGS aged 19-35 years (placebo, n=23; FFA 0.2mg/kg/day, n=18; FFA 0.7mg/kg/day, n=16). Everyday EF was evaluated using the Behavior Rating Inventory of Executive Function®—Adult Version (BRIEF®-A). Clinically meaningful improvement and worsening were defined using Reliable Change Index ≥90% and ≥80% certainty, respectively, and calculated using cross-tabulations and Somers’ D (p≤0.05); if significant, two-sided Fisher’s Exact tests were performed (p≤0.05).

Results Treatment and the likelihood of improvement were associated in the Behavior Regulation Index (BRI), Metacognition Index (MI), and Global Executive Composite (GEC). FFA 0.7 mg/kg/day showed a greater likelihood of improvement than placebo in MI. Treatment and likelihood of improvement were associated in 3 of 4 BRI and 3 of 5 MI scales. FFA 0.7 mg/kg/day showed a greater likelihood of improvement than placebo in the Inhibit, Initiate, Task Monitor, and Organization of Materials scales. FFA 0.2mg/kg/day showed a greater likelihood of improvement than placebo in the Shift scale. No clinically meaningful worsening was detected with treatment.

Conclusions FFA was associated with clinically meaningful improvements in everyday EF in adults with LGS over a relatively short treatment period. Higher-dose FFA showed a greater likelihood of improvement in everyday cognitive regulation, driven by amelioration in initiating, task monitoring, and organizing materials. Treatment with FFA initiated in adulthood may confer benefits in everyday EF.

Authors/Disclosures
Kelly G. Knupp, MD (Children's Hospital Colorado) PRESENTER	The institution of Dr. Knupp has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony. Dr. Knupp has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsy Research.
Kim I. Bishop, PhD (Global Pharma Consultancy, LLC)	Dr. Bishop has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for zogenix. Dr. Bishop has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Medtronic. Dr. Bishop has stock in zogenix.
	No disclosure on file
	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.
Ingrid E. Scheffer, MBBS, PhD, FRACP, AO (Melbourne Brain Centre)	Dr. Scheffer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals, Inc. Dr. Scheffer has received personal compensation in the range of $0-$499 for serving as a Consultant for Longboard Pharmaceuticals . Dr. Scheffer has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Scheffer has received personal compensation in the range of $0-$499 for serving as a Consultant for Biocodex. 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 Einstein Visiting Fellowship. The institution of Dr. Scheffer has received research support from National Health and Medical Research Council, Australia. 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 $0-$499 for serving as a Speaker honoraria with Akumentis. Dr. Scheffer has received personal compensation in the range of $0-$499 for serving as a Speaker honoraria with Biocodex. Dr. Scheffer has received personal compensation in the range of $0-$499 for serving as a Speaker honoraria with Chiesi . Dr. Scheffer has received personal compensation in the range of $0-$499 for serving as a Travel/Conference/Speaker honoraria with Stoke Therapeutics. Dr. Scheffer has received personal compensation in the range of $0-$499 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 Biohaven Ltd. 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 Bright Minds 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 Neuren Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Praxis Precision Medicines 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 Epileptic Disorders 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 Journal Editorial Board with The Lancet Neurology 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. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Shanghai Zhimeng Biopharma 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 with Supernus Pharmaceuticals that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with UCB Biopharma SRL that is relevant to AAN interests or activities. Dr. Scheffer has a non-compensated relationship as a Trial investigator with Ultragenyx that is relevant to AAN interests or activities.
	No disclosure on file
J. Helen Cross (UCL-Institute of Child Health)	Dr. Cross has nothing to disclose.
Renzo Guerrini (Hotelplan)	Renzo Guerrini has nothing to disclose.
	No disclosure on file
Gerard A. Gioia, MD	Dr. Gioia has received personal compensation in the range of $0-$499 for serving as a Consultant for Global Pharma Consultancy. Dr. Gioia has received publishing royalties from a publication relating to health care.
	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.

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