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Abstract Details

Profound Reduction in Seizure Frequency (=75%) Leads to Improved Everyday Executive Function in Patients with Dravet Syndrome at 1 Year Post-treatment with ZX008 (Fenfluramine HCl Oral Solution): Analysis of Data From the Phase 3 Clinical Development Program
Epilepsy/Clinical Neurophysiology (EEG)
P12 - Poster Session 12 (12:00 PM-1:00 PM)
12-006
To evaluate the relationship between changes in monthly convulsive seizure frequency (MCSF) and executive function in patients with Dravet syndrome (DS) after 1 year of add-on fenfluramine in an open label extension (OLE) study (NCT02823145).
Patients with DS experience frequent, pharmacoresistant seizures beginning in infancy and develop cognitive impairment over time. Long-term studies have not evaluated whether MCSF reduction correlates with improved executive function, an important aspect of behavioral, emotional, and cognitive functioning.
Patients with DS (ages 5-18 years) were randomized to fenfluramine (0.2-0.7 mg/kg/day) or placebo for 14-15 weeks in one of two phase 3 clinical studies. Patients entering the OLE received 0.2 mg/kg/day fenfluramine, then were titrated to effect. Executive function was evaluated by Behavior Rating Inventory for Executive Function (BRIEF®2) caregiver ratings. Change in BRIEF®2 component scores from double-blind baseline to Year 1 was compared with MCSF reduction by Spearman’s Rho correlation coefficients. BRIEF®2 rating changes in patients achieving <25% vs ≥75% MCSF reduction were assessed via Wilcoxon-Mann-Whitney test.
BRIEF®2 ratings were available from caregivers of 72 of 206 randomized patients (mean patient age [±SD], 11±4 years; 58% male). Median change in MCSF from pretreatment baseline to Year 1 was -64.0% (range: -99.7%-55.0%). Change in MCSF correlated significantly with global executive composite (GEC; r=0.23, P=0.05), and tended to correlate with behavior and emotion regulation indices (BRI, r=0.23, P=0.06; ERI, r=0.22, P=0.07) but not cognitive regulation index (CRI, r=0.18, P=0.14). Patients achieving ≥75% MCSF reduction were significantly more likely to experience improvements in BRI, ERI, and GEC scores than the <25% group (P<0.05).

This analysis identified a significant association between MCSF reduction and improved executive function. Profound (≥75%) reduction in MCSF was associated with greater self-regulation. Greater seizure reduction with treatment may improve everyday executive function over time in patients with DS.
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.
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..