Abstract Details

Title Long-Term (2-Year) Safety and Efficacy of Adjunctive ZX008 (Fenfluramine Hydrochloride Oral Solution) for Dravet Syndrome: Interim Results of an Ongoing Open-Label Extension Study

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S31 - Epilepsy/Clinical Neurophysiology (EEG) 3 (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Objective To evaluate the long-term safety and efficacy of long-term fenfluramine (FFA) as an adjunctive antiepileptic drug for treating patients with Dravet syndrome.

Background A previous interim analysis demonstrated that 64.4% of patients achieved clinically meaningful (≥50%) reduction in monthly convulsive seizure frequency (MCSF) after a median 256 days of treatment. This current analysis examines the magnitude, consistency, and durability of effect of FFA up to 2 years.

Design/Methods Patients who completed phase 3 controlled studies enrolled in an open-label extension (OLE) study (NCT02823145). Patients started at 0.2 mg/kg/day FFA and were titrated to effect (maximum: 26 mg/day, or 17 mg/day with stiripentol). Seizure frequency was captured via hand-held e-diary. Effectiveness and safety were assessed at each office visit (monthly for the first 3 months, then every 3 months).

Results At time of analysis (2/15/2019), 330 patients were enrolled (mean±SD age: 9.0±4.6 years old [y/o]; 55% male; 28% <6 y/o), with a median treatment duration of 445 days (range: 7-899 days). At 2 years on treatment, median MCSF change was -83.3% compared with the pre-fenfluramine treatment, core-study baseline (P<0.001). Over the entire treatment period, 62% of patients experienced clinically meaningful (≥50%) and 37% experienced profound (≥75%) reductions in MCSF. Most common (≥15%) non-cardiovascular TEAEs were nasopharyngitis (23%), pyrexia (23%), decreased appetite (21%), and diarrhea (15%). At the most recent visit, 8% of patients experienced a ≥7% weight loss while 39% gained ≥7% weight vs baseline in the core studies. There were no echocardiographic or clinical observations of valvular heart disease or pulmonary hypertension at any time during the OLE.

Conclusions Fenfluramine provided durable, clinically meaningful reduction in MCSF for up to 2 years of treatment and was generally well tolerated. FFA may represent an important new treatment option for patients with Dravet syndrome.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
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.
Elaine C. Wirrell, MD, FAAN (Mayo Clinic/Dept of Child Neurology)	Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Encoded. Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Dr. Wirrell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine. Dr. Wirrell has received publishing royalties from a publication relating to health care.
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
Glenn Morrison, PhD (Annexon Biosciences)	Dr. Morrison has received personal compensation for serving as an employee of Alector. Dr. Morrison has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG . Dr. Morrison has stock in Alector. Dr. Morrison 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..
Elizabeth Thiele, MD (Massachusetts General Hospital)	Dr. Thiele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GW Pharma/Jazz. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zogenix/UCB. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for nobelpharma. An immediate family member of Dr. Thiele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Thor labs. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for takeda. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for livanova. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Azurity. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus Pharmaceuticals. The institution of Dr. Thiele has received research support from GW Pharma/Jazz. The institution of Dr. Thiele has received research support from Zogenix/UCB. The institution of Dr. Thiele has received research support from Stoke Therapeutics.

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