Fenfluramine may effectively treat convulsive seizures among patients with Dravet syndrome (DS), according to a study recently published in Epilepsia.
“The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome,” the authors wrote.
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Conducted as part of the fenfluramine development program, this research encompassed 2 identical phase 3 clinical trials. These multinational trials aimed to evaluate the impact of this drug on convulsive seizures among patients with DS. The trials took place in North America, Western Europe, and Australia.
The study enrolled patients who are 2 to 18 years of age with a clinical diagnosis of DS whose seizures were not adequately controlled by their current antiseizure medication regimen. Participants underwent genetic testing to confirm the presence of a likely pathogenic variant of SCN1A. During a 6-week baseline period, the investigators established participants’ baseline seizure frequency to determine their eligibility for randomization.
Patients were then randomized into 3 treatment groups: placebo, 0.2 mg/kg/day of fenfluramine, or 0.7 mg/kg/day of fenfluramine. The study’s primary endpoint was a comparison of the change in mean monthly convulsive seizure frequency (MCSF) from baseline to the titration-maintenance period for patients treated with 0.7 mg/kg/day of fenfluramine compared to those receiving placebo. The study also explored secondary outcomes, including the percentage of patients achieving at least a 50% reduction in MCSF and the longest seizure-free intervals in each group.
Results demonstrated that patients treated with fenfluramine experienced significant reductions in MCSF compared to those on placebo. Specifically, patients on 0.7 mg/kg/day of fenfluramine showed a 73% clinically meaningful reduction (≥50%) in MCSF, with 48% experiencing a profound (≥75%) decrease. Furthermore, these patients enjoyed longer seizure-free intervals. Both caregivers and investigators reported greater improvements among patients treated with fenfluramine compared to placebo.
Importantly, fenfluramine’s safety profile was positive. The most common adverse events were consistent with known effects of the drug, such as decreased appetite and somnolence. There were no incidents of valvular heart disease or pulmonary artery hypertension during the study.
“However, most patients with DS who completed this or other double-blind studies of fenfluramine have enrolled in an open-label extension study, during which it was demonstrated that the benefits of fenfluramine have been sustained for a median of 631 days,” the authors highlighted.
Sullivan J, Lagae L, Cross H, et al. Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial. Epilepsia. Published online August 06, 2023. doi:10.1111/epi.17737