Abstract Details

Title Fenfluramine Improves Everyday Executive Functioning in Patients With Lennox-Gastaut Syndrome: Analysis of Phase 3 Data

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-004

Background Adjunctive fenfluramine reduced seizure frequency and improved everyday EF in patients with Dravet syndrome or LGS in RCTs and/or long-term extension studies.

Objective To evaluate dose-response relationships for the impact of fenfluramine on everyday executive function (EF) in post-hoc analyses of data from a 14-week randomized controlled trial (RCT) of patents with Lennox-Gastaut syndrome (LGS).

Design/Methods Patients with LGS received placebo or fenfluramine (0.2 or 0.7mg/kg/day) for 14 weeks. EF was evaluated at baseline and Week 14 for patients aged 5-18 years with the Behavior Rating Inventory of EF® (BRIEF® 2) parent form; (Behavior Regulation Index, BRI; Emotion Regulation Index, ERI; Cognitive Regulation Index, CRI; Global Executive Composite, GEC). Clinically meaningful improvement in BRIEF®2 indexes/composite T-scores from baseline to Week 14 was defined as a Reliable Change Index (RCI) of ≥95% certainty. Associations between treatment groups and clinically meaningful change were evaluated using Somers’ D; post-hoc tests were calculated by Fisher’s Exact tests (two-sided ≤0.05).

Results

Data were analyzed for 137 patients (placebo, n=45; fenfluramine 0.2mg/kg/day, n=45; fenfluramine 0.7mg/kg/day, n=47; median age, 12-13 years). Median baseline T-scores were clinically elevated across treatment groups (T≥65) for BRI (T=66), CRI (T=65), and GEC (T=67). There was a significant association between treatment groups and clinically meaningful improvement in BRI (placebo: 13.3%; 0.2mg/kg/day: 17.8%; 0.7mg/kg/day: 29.8%; p=0.05), with a trend for FFA 0.7mg/kg/day to show a greater likelihood of improvement than placebo (p<0.08). There were trends toward associations between increasing treatment levels and clinically meaningful improvement in CRI (placebo: 13.3%; 0.2mg/kg/day: 26.7%; 0.7mg/kg/day: 27.7%; p=0.09) and GEC (placebo: 11.1%; 0.2mg/kg/day: 24.4%; 0.7mg/kg/day: 25.5%; p=0.07).

Conclusions Patients in this LGS population showed an association between increasing FFA dose and increasing improvement in EF domains of behavior regulation, and a similar tendency for cognitive regulation and global executive composite.

Authors/Disclosures
Kim I. Bishop, PhD (Global Pharma Consultancy, LLC) PRESENTER	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
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.
Kelly G. Knupp, MD (Children's Hospital Colorado)	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.
	No disclosure on file
	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..