Joseph E.Sullivan, MD
Data from an open-label, phase 3 clinical study of adjunctive fenfluramine (Fintepla; Zogenix) demonstrated an association between a significant reduction in convulsive seizure frequency and improvement in everyday executive function in patients with Dravet syndrome (DS). The findings were presented at the 2019 American Epilepsy Society Annual Meeting, December 6-10, 2019 in Baltimore, Maryland.
In late November, the FDA accepted the new drug application for the oral solution of fenfluramine for the treatment of seizures associated with DS. Additional studies on the drug have shown that it can be an effective treatment option for patients with DS taking stiripentol who continue to have seizures.
The double-blind, parallel-group, placebo-controlled, open-label, phase 3 extension study examined fenfluramine in 53 patients (ages 2-18 years) with DS. The trial aimed to evaluate the overall relationship between changes in convulsive seizure frequency and executive function as well as the impact of profound (>=75%) and minimal (<25%) changes in convulsive seizure frequency on these outcomes.
READ MORE: PHASE 3 TRIAL OF FENFLURAMINE IN LENNOX-GASTAUT SYNDROME COMPLETES ENROLLMENT
Executive function was evaluated based on score on the Behavior Rating Inventory of Executive Function (BRIEF), which was taken at baseline, and later updated to BRIEF2, including the Behavior Regulation Index (BRI), Emotion Regulation Index (ERI), Cognitive Regulation Index (CRI), Global Executive Composite, and Global Executive Composite (GEC) scores.
From baseline, patients who had year 1 BRIEF2 data and had ³1 year of fenfluramine exposure (n=53) saw a -71.0% change in convulsive seizure frequency (range, -99.7%-55.0%). Among the participants, 24 (45%) achieved a ³75% reduction in convulsive seizure frequency compared to 11 patients who had <25% reduction in convulsive seizure frequency. The investigators observed a correlation between ERI (P = .032), GEC (P = .034) and CRI (P = .066) with change in convulsive seizure frequency. Meaningful improvements on ERI and GEC (P < .05) are paralleled with the higher percentage of patients who experienced profound changes in convulsive seizure frequency.
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Bishop KI, Isquith PK, Gioia G, et al. Profound reduction in seizure frequency (>75%) leads to improved everyday executive function: analysis from a phase 3 study of ZX008 (fenfluramine HCL) in children/ young adults with Dravet syndrome. Presented at: American Epilepsy Society 2019 Meeting. December 6-10, 2019; Baltimore, Maryland. Abstract 2.438.