Fenfluramine treatment beyond dravet and lennox-gastaut syndromes - A retrospective study suggesting a novel use in genetic, developmental and epileptic encephalopathies (DEEs).

INTRODUCTION

Fenfluramine (FFA), an amphetamine derivative, was historically used as an appetite suppressant but was discontinued for its association with valvular heart disease and pulmonary hypertension. More recently, significant results in randomized trials demonstrated promising seizure reduction properties. Further research led to FDA approval for usage of FFA in children aged two years and older with Dravet syndrome (DS) in 2020 and Lennox-Gastaut syndrome (LGS) in 2022 [1,2]. Considering FFA's success in these populations, we aimed to characterize the extent of its efficacy related to drug-resistant epilepsy in individuals with genetic developmental and/or epileptic encephalopathies (DEEs). We hypothesized similar rates of improvement (at least 25 % seizure reduction) as the LGS and DS studies.

METHODS

After Institutional Review Board approval, a systematic retrospective chart review was conducted of pediatric patients with DEE receiving clinical care in Boston Children's Hospital, Cohen Children's Medical Center, and Our Lady of the Lake Children's Hospital-Baton Rouge systems who were placed on FFA after July 1, 2020. Self-reported seizure frequency and side effects were extracted. Reduction in monthly seizure frequency was the primary outcome investigated. Related-Samples Wilcoxon Signed Rank Test was performed to evaluate mean difference in seizure frequency pre-and-post-FFA treatment. The patients in this sample were on FFA for a duration of 23.5 ± 15.1 months.

RESULTS

There were 20 children with epilepsy of diverse etiologies (excluding LGS and DS) who were placed on FFA and met our inclusion criteria. A statistically significant (p = 0.02) decrease in seizure frequency in days per month was found, with a mean reduction of 4.6 days per month. For generalized seizure types, there was a median reduction of 7 days per month. Some children responded more dramatically than others with 95 % seizure reduction in our two children with apneic seizures and tuberous sclerosis. Nine of twenty children observed had at least 50 % seizure reduction, 8 of which had at least 75 % seizure reduction. Additionally, the safety profile of FFA was similar as the one reported in the studies done on patients with DS and LGS.

CONCLUSIONS

This retrospective report suggests that FFA may be an effective add-on therapeutic option in children with rare, genetic epilepsies where efficacy was notable early on in drug initiation and titration. A trial of FFA for drug-resistant seizures may be considered to assess efficacy in the DEE population beyond DS and LGS.