|The following article is part of conference coverage from the American Epilepsy Society’s Annual Meeting in New Orleans, LA. The Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2018.|
NEW ORLEANS — Children with Dravet syndrome who received 0.2 mg/kg and 0.8 mg/kg doses of fenfluramine experienced clinically meaningful improvements in emotional and behavioral regulation, as well as improvements in planning and organization abilities, according to research findings presented at the 2018 American Epilepsy Society meeting held November 30-December 4, 2018.
“Fenfluramine HCl has demonstrated superior efficacy compared with placebo for the reduction in frequency of convulsive seizures in children and young adults… with Dravet syndrome in 2 recently completed Phase 3 double-blind, placebo-controlled clinical trials,” the study investigators wrote. “Patients with epileptic encephalopathies, such as Dravet syndrome, 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 Dravet syndrome in a Phase 3 placebo-controlled trial.”
Following a 6-week baseline period, a total of 77 patients with Dravet syndrome (age range, 2 to 18) were randomly assigned to either placebo (n=25), 0.2 mg/kg/day fenfluramine (n=24), or 0.8 mg/kg/day fenfluramine (n = 28). Caregivers of patients age ≥5 completed the Behavior Rating Inventory of Executive Function (BRIEF®2). The researchers investigated changes from baseline to the end of the study in several different mental faculties.
The treatment groups demonstrated significant and clinically meaningful improvements in the BRIEF indexes vs the placebo group (P <.02). In addition, a significantly greater improvement on the Plan/Organize scale of the Cognitive Regulation Index was associated with fenfluramine vs placebo (P <.04). No differences were observed between groups with regard to worsening of mental faculties and capabilities.
“Theoretical and empirical models support that improved emotional control and behavioral regulation serve as ‘building blocks’ to then enable higher level cognitive regulation functions,” the researchers added. “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.”
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Bishop KI, Gioia GA, Isquith PK, et al. Improved everyday executive function with fenfluramine hcl oral solution (Fintepla®): results from a phase 3 study in children and young adults with Dravet syndrome. Presented at: AES 2018; November 29-December 4, 2018; New Orleans, Louisiana. Poster 2.454.