Dravet Children’s Behavioral, Emotional Gains Tied to Fintepla

Researchers looked at data from 61 children, aged 2–4

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Fintepla (fenfluramine) is associated with dose-dependent, clinically meaningful improvements in everyday behavioral and emotional control, as well as the ability to adapt to new situations, in preschool-aged children with Dravet syndrome.

These benefits weren’t always tied to a clinically meaningful reduction in the frequency of seizures, suggesting the therapy may directly affect this patient population’s cognitive skills.

These are the findings of a posterior analysis of data from two completed Phase 3 clinical trials that supported the therapy’s approval in children and adults with Dravet.

The study, “Fenfluramine treatment is associated with improvement in everyday executive function in preschool-aged children (<5 years) with Dravet syndrome: A critical period for early neurodevelopment,” was published in Epilepsy and Behavior.

Dravet syndrome is a type of epilepsy marked by episodes of prolonged seizures starting in the first year of life. During preschool years, many children with the disease develop deficits in everyday executive function, the set of cognitive abilities needed for self-control, flexible thinking, and coordinating behavior, emotion, and cognitive capabilities.

These deficits make it critical to have an early intervention to prevent the disease’s impact on behavioral, emotional, and cognitive processes later in life.

Developed by Zogenix, now part of UCB, Fintepla is approved for treating seizures in adults and children 2 and older with Dravet. Data from previous Phase 3 trials showed that besides reducing seizure frequency, the therapy is associated with executive function improvements in patients aged 5 to 18. These post hoc analyses, done after the trials ended, didn’t assess everyday executive function changes in the 2- to 4-year-olds who participated.

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Fintepla’s effect on young children’s executive function

The researchers analyzed available executive function data from 61 children of these ages with Dravet syndrome who participated in two Phase 3 trials (NCT02682927 and NCT02926898) that tested Fintepla against a placebo.

The children’s median age was 3, and 54% were boys. A total of 39 were treated with Fintepla and 22 a placebo for little over three months. All received standard of care.

Fintepla was given at a daily dose of 0.2 mg/kg to 15 children, 0.4 mg/kg to 10 children along with the anti-seizure medication Diacomit (stiripentol), and 0.7 mg/kg — the currently approved maximum recommended dose — to 14 children.

Everyday executive function was evaluated via parent ratings on the Behavior Rating Inventory of Executive Function—Preschool Version (BRIEF–P). This measure consists of 63 items that form three broad indexes — Inhibitory Self-Control, Flexibility, and Emergent Metacognition — and one composite score, Global Executive Composite (GEC).

The Inhibitory Self-Control Index reflects the ability to control behavior and emotions. The Flexibility Index reflects the ability to adapt behaviorally and emotionally to new situations. The Emergent Metacognition Index reflects the ability to problem-solve.

At the beginning of the study, most children across all groups (60–81.8%) showed impairments in overall executive function, based on GEC scores.

Self-control and problem solving were the most frequently affected skills, reported in 54.5–86.4% of children in each group. Flexibility was impaired in about 33% of them.

Treatment with Fintepla resulted in clinically meaningful improvements in at least one BRIEF-P index in 17 of the 61 children (28%). The therapy’s effect was dose-dependent.

Specifically, most children (64%) in the 0.7 mg/kg daily dose group achieved such improvements compared with 30% in the 0.4 mg/kg group, 20% in the 0.2 mg/kg group, and 9% in the placebo group.

Compared with the placebo group, a significantly greater proportion of patients in the higher dose group showed reliable, clinically meaningful improvements in self-control (50% vs. 5%), flexibility (36% vs. 0%), and GEC (36% vs. 0%). Differences in problem-solving, while favoring the therapy (29% vs. 5%), failed to reach statistical significance.

Observed executive function improvements didn’t always correspond to a relevant reduction in seizure frequency since only seven of the 17 children with such improvements also showed a clinically meaningful reduction (at least 50% or more) in monthly seizure frequency. This included six of the 14 children in the 0.7 mg/kg/day-dose group.

These gains were “not entirely due to seizure frequency reduction,” which suggests Fintepla may directly affect everyday executive function “during the early formative years of neurodevelopment,” the researchers said.