Fenfluramine HCl has demonstrated superior efficacy compared with placebo for the reduction in frequency of convulsive seizures in children and young adults (2-18 years old) with Dravet syndrome (DS) in two recently completed Phase 3 double-blind, placebo-controlled clinical trials. Patients with epileptic encephalopathies, such as DS, also have impairment in cognition and neurodevelopment, which is believed to be in part due to the frequency of poorly treated seizures. Here we provide an analysis of the impact of fenfluramine on caregiver-reported everyday executive functioning of their children with DS in a Phase 3 placebo-controlled trial.
Patients in the fenfluramine 0.2 mg/kg and 0.8 mg/kg groups showed significant and clinically meaningful improvements in behavior regulation, emotion regulation, and planning and organization. Theoretical and empirical models support that improved emotional control and behavioral regulation serve as “building blocks” to then enable higher level cognitive regulation functions. Children and young adults must be able to inhibit impulses, modulate emotions, and adapt flexibly to changes before they can demonstrate or develop cognitive regulatory functions, including working memory, planning, and organization. The impact of behavior and emotion regulation might be expected to enable improvements in the higher level cognitive regulation with longer-term treatment and will be examined in the long-term extension study of fenfluramine.