Fenfluramine appears effective in Lennox-Gastaut syndrome
Patients with Lennox-Gastaut syndrome (LGS) treated with fenfluramine had a significantly greater reduction in drop seizures compared to patients receiving placebo, according to the results of a clinical trial.
In this multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial, aged 2 to 35 years with confirmed diagnosis of LGS and experienced ≥2 drop seizures per week during the 4-week baseline were randomized to receive 0.7-mg/kg/d fenfluramine (n = 87), 0.2-mg/kg/d fenfluramine (n = 89), or placebo (n = 87).
In the 0.7-mg/kg/d fenfluramine group, the median frequency of drop seizures was 26.5 percentage points; in the 0.2-mg/kg/d fenfluramine group there was a 14.2 percentage points; and in the placebo group a 7.6 percentage points.
The trial met its primary efficacy end point with patients in the 0.7-mg/kg/d fenfluramine group achieving a -19.9 percentage points estimated median difference in drop seizures from baseline versus the placebo group.
A ≥50% response was achieved in 25% of patients in the 0.7-mg/kg/d fenfluramine group compared to 10% in the placebo group.
A much improved or very much improved rating on the Clinical Global Impression of Improvement scale was given to more patients in the 0.7-mg/kg/d fenfluramine group by site investigators and caregivers than patients in the placebo group (26% vs 6%).
Generalized tonic-clonic seizure subtype appeared to be the most responsive to fenfluramine with 46% response. There was a decrease in the frequency of 45.7% in the 0.7-mg/kg/d fenfluramine group and 58.2% in the 0.2-mg/kg/d fenfluramine group and an increase of 3.7% in the placebo group.
The most common treatment-emergent adverse events included decreased appetite in 22%, somnolence in 13%, and fatigue in 13%. There were no cases of valvular heart disease or pulmonary arterial hypertension reported.
Knupp KG, Scheffer IE, Ceulemans B, et al. Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2022;doi: 10.1001/jamaneurol.2022.0829. Epub ahead of print. PMID: 35499850.