Abstract Details

Title Real-world Experience with ZX008 (Fenfluramine HCl) for the Treatment of Seizures in Dravet Syndrome: Initial Report from United States Expanded Access Program

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S59 - Epilepsy/Clinical Neurophysiology (EEG) 4 (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Objective To describe the effectiveness and safety of fenfluramine treatment in patients with refractory Dravet syndrome (DS) in an expanded access program.

Background Two recent Phase 3 clinical trials found that fenfluramine (administered as oral solution of fenfluramine HCl containing 2.2 mg/mL fenfluramine) added to current antiepilepsy drug (AED) regimens at doses between 0.2 and 0.7 mg/kg/day significantly reduced convulsive seizure frequency and improved clinical status of patients with DS.

Design/Methods This program is open to US-residing patients with DS who do not qualify for participation in the ongoing fenfluramine clinical trials. All patients initiated fenfluramine treatment at 0.2 mg/kg/day for 14 days; thereafter, doses could be adjusted based on effectiveness and tolerability to a maximum of 0.7 mg/kg/day (not to exceed 26 mg/day) or in patients treated with stiripentol to a maximum 0.4 mg/kg/day (not to exceed 17 mg/day). A 7-point Likert scale was used by the treating physician to assess improvement in global clinical status, cognition, behavior, and motor abilities.

Results Twenty-three patients (61% female, mean age=6.8 years [range, 2-22]) have enrolled and been treated for a median of 90 days [range, 30-180]. The most common concomitant AEDs were clobazam, valproate, stiripentol, and cannabidiol. Fifteen (65%) patients were reported as experiencing meaningful global clinical improvement based on a rating of “very much improved” or “much improved.” Similarly, improvements in cognition, behavior, or motor abilities were experienced by 56%, 43%, and 48%, respectively. The most common adverse events (AEs; in ≥10% patients) included fever (30%), decreased appetite (17%), and emesis (13%). The majority were mild-to-moderate in intensity. No patient developed valvular heart disease or pulmonary arterial hypertension nor discontinued due to an AE.

Conclusions DS patients treated with fenfluramine in a “real-world” setting demonstrated clinically meaningful responses similar to those observed in clinical trials. Fenfluramine was generally well-tolerated; no patient developed any cardiovascular AEs.

Authors/Disclosures
Scott Perry PRESENTER	No disclosure on file
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.
David B. Burkholder, MD, FAAN (Mayo Clinic)	The institution of Dr. Burkholder has received research support from Longboard pharmaceuticals.
	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..

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