Abstract Details

Title Stratified Effectiveness and Safety of Fenfluramine in Dravet and Lennox-Gastaut Syndromes: A Retrospective Comparative Analysis of Trial and Open-label Extension Data (2018-2024)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-010

Objective
To assess the age stratified and adjunctive therapy specific effectiveness and safety of fenfluramine in patients with Dravet and Lennox Gastaut syndromes using retrospective comparative analysis of trial and open label extension data from 2018 to 2024.

Background Fenfluramine(FFA) is a serotonergic antiseizure medication approved for the treatment of Dravet syndrome(DS) and Lennox Gastaut syndrome(LGS). While randomized and open label studies have established its efficacy, the comparative effectiveness and safety across different age groups and adjunctive therapy conditions remain insufficiently defined. Emerging pooled evidence also indicates a sustained therapeutic benefit in both pediatric and adult populations, supporting its evolving role in developmental and epileptic encephalopathies.This retrospective synthesis integrates data from multiple clinical trials and extension studies to characterize age related and therapy specific outcomes.

Design/Methods A comprehensive search was conducted in PubMed, Scopus, and Web of Science for studies published between 2018-2024, including randomized controlled trials and open-label extensions.Only seven studies were eligible for the criteria.Data were extracted from peer-reviewed tables and supplementary datasets. Outcomes included median percent seizure-frequency reduction, =50% and =75% responder rates, and adverse-event (AE) profiles. Results were descriptively compared across DS and LGS by age (<6 y, 6-17 y. =18 y) and stiripentol (STP) co-therapy by using IBMSPSS V 29.

Results Among 900 patients,In DS, long-term OLE data (n = 374; median exposure 824 days) showed a median -66.8% reduction in monthly convulsive seizure frequency (MCSF); those on STP had -36.2%, and those without STP-71.6% . In the European Early Access Program (<6 y n = 63; 6-17 y n = 62; =18 y n = 24), =75% seizure-frequency reduction occurred in 62%, 53%, and 50% at 3 months, and 55%, 46%, and 80% at 12 months .In LGS, the phase 3 RCT (n = 263) demonstrated median drop-seizure reductions of -26.5% (0.7 mg/kg/day) and -14.2% (0.2 mg/kg/day) versus -7.6% for placebo, with =50% responder rates =25% vs 10% placebo.The LGS OLE (n = 247) sustained =-51.8% median reduction at 12 months, with 51% achieving 250% response.Common AEs were decreased appetite (16-25%), somnolence (13-20%), and fatigue (10-13%); no valvular heart disease or pulmonary arterial hypertension were reported.

Conclusions Fenfluramine provides durable seizure reductions and consistent safety across DS and LGS, with the strongest benefit observed in younger and STP-naïve patients. The absence of cardiac toxicity across ~1,000 patient-years supports its long-term safety. Stratified synthesis of multi-trial evidence enables precision use of FFA in developmental and epileptic encephalopathies.

Authors/Disclosures
Akash Rawat, MD, MBBS PRESENTER	Dr. Rawat has nothing to disclose.
Shreya Singh Beniwal, MBBS	Miss Beniwal has nothing to disclose.
Anam Sayed Mushir Ali, MBBS	Dr. Sayed Mushir Ali has nothing to disclose.
Rafael Everton A. da Costa, MD	Dr. da Costa has nothing to disclose.
Abhishek Mehan, MBBS	Dr. Mehan has nothing to disclose.
Raghabendra kumar Mahato, Medical Student	Mr. Mahato has nothing to disclose.
Julia Franco Neiva, Student	Miss Franco Neiva has nothing to disclose.

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