Fenfluramine: an effective treatment for developmental epileptic encephalopathies beyond Dravet and Lennox-Gastaut Syndromes.

backgroundFenfluramine (FFA) is an antiseizure medication (ASM) with effectiveness in Dravet Syndrome (DS) and Lennox-Gastaut syndrome (LGS), but unknown effectiveness in other developmental epileptic encephalopathies (DEEs).

methodsThis multicenter, retrospective study evaluated the efficacy and tolerability of FFA in children with DS, LGS and other DEEs within clinical practice. Data were extracted from patients' charts before and up to 6 months after treatment.

resultsFifty-four patients (median age 10 years; 67% male) with DS (n = 17), LGS (n = 20), or other DEE (n = 17) were included. At three months following FFA treatment, the proportion of responders (≥ 50% reduction in seizure frequency) was significantly higher in patients with DS (94%) compared with LGS (50%; p = 0.003) and other DEEs (47%; p = 0.003). No significant difference in responder rates was observed between the LGS and other DEE groups. FFA efficacy was independent of dosage, concomitant ASMs, epilepsy duration, etiology, or specific comorbidities. FFA demonstrated effectiveness across all seizure types, with particular efficacy in tonic-clonic seizures. Responders experienced improvements in physician-assessed seizure intensity; 56-91% showed improvements in other Clinical Global Impression domains, including cognition, behavior, sleep, and seizure severity. Adverse events occurred in 56% of patients and were predominantly mild, with somnolence, anorexia, and irritability the most common. Treatment discontinuation due to AEs occurred in three patients (1 LGS, 2 other DEEs).

conclusionFFA demonstrates effectiveness and tolerability in patients with DEEs in a real-world setting, and has potential as a broad-spectrum ASM, effective across a wide range of DEEs, seizure types, and patient profiles.