Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome

Abstract

This randomized clinical trial examines the change from baseline in drop seizure frequency, response rates, and improvement on the Clinical Global Impression scale among patients with Lennox-Gastaut syndrome.

Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany

“…Of note, FFA has also shown efficacy in reducing seizures in other drugresistant epilepsy syndromes including Lennox-Gastaut syndrome and CDKL5 deficiency disorder. 21,22 As well as reductions in total seizures and GTCSs, we found a statistically significant reduction in seizure days, in line with data from the pivotal RCTs that have reported increases in seizure-free days and statistically significant increases in seizure-free intervals. 6,7 In addition, FFA was associated with improvements in overall condition (physician-rated CGIC).…”

“…Furthermore, the ultimate treatment goal of seizure freedom or near freedom from seizures has been observed in a notable proportion of patients in our study (29.5% with ≤1 seizure per month) and others, 6,7,16 with Nabbout et al 7 reporting a statistically significant difference in the proportion of patients having ≤1 convulsive seizure during the 14‐week treatment period with FFA compared to placebo (Table ). Of note, FFA has also shown efficacy in reducing seizures in other drug‐resistant epilepsy syndromes including Lennox–Gastaut syndrome and CDKL5 deficiency disorder 21,22 …”

Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine

“…Most frequent adverse events (at least 10%) included decreased appetite, somnolence, fatigue, vomiting, diarrhea and pyrexia. No cardiovascular complications were reported ( Knupp 2021a ). After completion of the randomized-controlled phase, patients were enrolled in the open-label extension study and received FFA twice daily for up to 1 year.…”

Fenfluramine: A Review of Pharmacology, Clinical Efficacy, and Safety in Epilepsy

“…A multicenter, double-blind, placebo-controlled RCT was conducted in 263 LGS patients (2–35 years old) with ≥2 drop seizures/week [ 69 ] ( Figure 2 ). The median percentage reduction in frequency of drop seizures was 26.5% ( p < 0.01) with 0.7-mg/kg/d, 14.2% ( p = 0.09) with 0.2-mg/kg/d, and 7.6% in the placebo group during 14 weeks of the treatment period.…”

“…More patients in the 0.7-mg/kg/d group than in the placebo group had ‘much improved’ or ‘very much improved’ ratings on the Clinical Global Impression of Improvement scale (26% vs. 6%; p =.001). Following completion of the phase 3 RCT, 247 patients enrolled for the open-label extension study [ 70 ]. Interim analysis at one year showed that 83 patients (33.6%) discontinued taking FFA in the interval.…”