Rationale:
Fenfluramine was licenced in the UK for the treatment of seizures in children and adults with Lennox Gastaut Syndrome (LGS) in March 2025.
We have the largest UK cohort of adults with LGS for whom Fenfluramine was approved on compassionate grounds due to the highly refractory nature of their epilepsy. We describe their clinical course and response to adjunctive Fenfluramine over a two year period 2023-2025.
Methods:
All six patients (four female) aged between 22 and 34 years have a genetically confirmed Developmental and epileptic encephalopathy (DEE). Diagnoses include Alternating Hemiplegia of Childhood and CDKL5 – associated DEE. Five patients were experiencing daily convulsive seizures pre-Fenfluramine.
Four patients were non efficacious to VNS inserted in childhood. The minimum number of anti-seizure medications (ASMs) tried pre-Fenfluramine was 8.
Seizure types and frequency were obtained from caregiver diaries. Assessment of efficacy included reduction in use of rescue medications and reduction in hospitalisations.
Results:
All patients remained on Fenfluramine 4.4mg-17.2mg/ day at last follow up. 5 patients experienced a >50% reduction in rescue medications and these 5 patients additionally experienced a >75% reduction in seizure-related hospitalisations; both metrics reflected a reduction in convulsive seizures. 1 patient with seizure associated with CDKL5 experienced a < 50% reduction in seizure clusters.
No patients experienced valvular side effects. Fenfluramine was well tolerated without sedative side effects. Greatest efficacy was seen in those prescribed both Cenobamate and Fenfluramine. The ASM most commonly reduced following initiation of Fenfluramine was Cannabidiol.
Conclusions:
Fenfluramine appears to be efficacious in reducing convulsive seizures for those adults with highly refractory epilepsy in the context of LGS. Addition of Fenfluramine contributed to a substantial reduction in hospitalisations, with associated health-economic benefits. Assessment of efficacy needs to be individualised to reflect the variability in seizure pattern and frequency in this highly refractory population.
Funding: None