Скачать или смотреть Evaluating Fenfluramine in Patients With Lennox-Gastaut Syndrome

Amelie Lothe, PhD, Global Medical Community Head for Rare Epilepsies at UCB, discusses recent data evaluating fenfluramine in patients with Lennox-Gastaut syndrome.

Developmental and epileptic encephalopathies (DEEs) are rare, severe, lifelong epileptic syndromes that greatly impact the daily lives of patients and their families. DEEs are commonly associated with drug-resistant seizures, cognitive and motor challenges, behavioral issues, high risk of premature death, and significant unmet needs. The most common DEEs are Dravet syndrome and Lennox-Gastaut syndrome (LGS).

LGS is characterized by multiple types of seizures and intellectual disability that begin in childhood. This condition can be caused by brain malformations, perinatal asphyxia, severe head injury, central nervous system infection and inherited degenerative or metabolic conditions. In about one-third of cases, no cause can be found.

Recent data presented at the European Paediatric Neurology Society (EPNS) 2025 meeting showed the effects of fenfluramine in patients with LGS. Fenfluramine is a dual-action small molecule that targets both the serotonergic and sigma-1 receptors.

Abstract 1

This post-hoc analysis examined the time of onset and duration of treatment-emergent adverse events (TEAEs) reported in the fenfluramine randomized controlled trial (NCT03355209) and open-label extension study in patients with LGS. Patients were randomized to fenfluramine 0.2 mg/kg/day or fenfluramine 0.7 mg/kg/day or placebo.

TEAEs occurring in 10% or greater of patients were diarrhea, vomiting, fatigue, pyrexia, decreased appetite, and somnolence. Patients in the 0.7 mg/kg/day group who experienced somnolence exhibited the earliest median time to onset of first occurrence of these TEAEs. Resolution of first occurrence of these TEAEs occurred in 45.2%-100% of patients treated with fenfluramine. First occurrence of pyrexia and vomiting resolved in all patients treated with fenfluramine 0.2 mg/kg/day.

In the open-label extension, decreased appetite was the TEAE with the earliest median time to onset and 72.5%-100% of patients experienced resolution.

Abstract 2

This abstract describes the final long-term safety and efficacy from a fenfluramine open-label extension study in patients with LGS. A total of 247 patients enrolled in the open-label study, with 158 reaching completion. Participants started on fenfluramine 0.2 mg/kg/day and then titrated to effectiveness and tolerability after one month.

The median treatment duration was 364 days and 83% of participants experienced one or more TEAE. Of 41 patients with one or more serious TEAE, 12 had one or more related to fenfluramine. TEAEs reported in 10% or greater of patients were decreased appetite, fatigue, nasopharyngitis, seizure, and pyrexia. Median decrease in frequency of seizures resulting in drop over the open-label extension was 29.5%. This analysis shows that fenfluramine was generally well-tolerated, with no new safety signals.

Chapters:
Introduction 00:00
Developmental and Epileptic Encephalopathies 00:59
Data on Fenfluramine 3:59