Fenfluramine safe, effective in convulsive episodes in kids with Dravet syndrome, finds clinical trial

In the present study, researchers have assessed the safety and efficacy of fenfluramine in treating convulsive seizures in patients with Dravet syndrome.

In this phase 3 clinical trial, patients aged 2-18 were enrolled. These children had poorly controlled convulsive seizures and were not also receiving stiripentol.

Eligible patients with a history of ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine 0.2 mg/kg/day, or fenfluramine 0.7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose, 26 mg/day).

Over two weeks, the doses were titrated and maintained for an additional 12 weeks.

The key results of this study are:

• Researchers screened 169 patients.
• A total of 143 patients were randomized to treatment.
• The mean age of these patients was 9.3±4.7 years, and 51% were male.
• The median baseline MCSF in the three groups ranged from 12.7-18.0 per 28 days.
• Patients on fenfluramine 0.7 mg/kg/day had a 64.8% greater reduction in MCSF than placebo.
• Following fenfluramine 0.7 mg/kg/day, 72.9% of patients had a ≥50% reduction in monthly convulsive seizure or MCSF. This was only 6.3% for the placebo group.
• The median most extended seizure-free interval was 30 days in the fenfluramine 0.7 mg/kg/day group compared with ten days in the placebo group.
• Some side effects were reduced appetite, somnolence, pyrexia, and decreased blood glucose. There was greater frequency in fenfluramine groups than in placebo.
• Researchers did not report any evidence of valvular heart disease or pulmonary artery hypertension.

The study has highlighted the role of fenfluramine as an anti-seizure in children with Dravet syndrome.

Further reading:

Sullivan J, Lagae L, Cross JH, Devinsky O, Guerrini R, Knupp KG, Laux L, Nikanorova M, Polster T, Talwar D, Ceulemans B, Nabbout R, Farfel GM, Galer BS, Gammaitoni AR, Lock M, Agarwal A, Scheffer IE; FAiRE DS Study Group. Fenfluramine in treating Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial. Epilepsia. 2023 Aug 6. doi: 10.1111/epi.17737.