Safety and Effectiveness of Fenfluramine for the Treatment of Seizures in Lennox-Gastaut Syndrome: Results from the Final Analysis of an Open-Label Extension Study

K. G. Knupp; A.-S. Schoonjans; J. Sullivan; L. Lagae; R. Guerrini; S. M. Zuberi; R. Nabbout; K. Riney; K. C. Nickels; R. Davis; M. D. Lock; D. Dai; T. Minh; R. Zhang Roper; A. Lothe; M. Langlois; S. Haas; A. Gil-Nagel

doi:10.1055/s-0045-1812136

Neuropediatrics, Table of Contents

Neuropediatrics 2025; 56(S 01): S1-S24
DOI: 10.1055/s-0045-1812136

Epilepsy

Safety and Effectiveness of Fenfluramine for the Treatment of Seizures in Lennox-Gastaut Syndrome: Results from the Final Analysis of an Open-Label Extension Study

Authors

K. G. Knupp

¹University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
A.-S. Schoonjans

²University Hospital Antwerp, Antwerp, Belgium
J. Sullivan

³Weill Institute for Neurosciences and Benioff Children's Hospital, University of California, San Francisco, San Francisco, California, United States
L. Lagae

⁴Member of the European Reference Network EpiCARE, Barcelona, Spain

⁵University of Leuven, Leuven, Belgium

⁶Leuven Childhood Epilepsy Center, Leuven, Belgium
R. Guerrini

⁷Meyer Children's Hospital IRCCS, Florence, Italy

⁸University of Florence, Florence, Italy
S. M. Zuberi

⁹Paediatric Neurosciences Research Group, School of Health & Wellbeing, University of Glasgow, Glasgow, United Kingdom

¹⁰Royal Hospital for Children, Glasgow, United Kingdom
R. Nabbout

⁴Member of the European Reference Network EpiCARE, Barcelona, Spain

¹¹Reference Centre for Rare Epilepsies, Necker Enfants Malades Hospital, APHP, Paris, France

¹²Institut Imagine, U 1163, Paris, France

¹³Université Paris Cité, Paris, France
K. Riney

¹⁴The University of Queensland, St Lucia, QLD, Australia

¹⁵Queensland Children's Hospital, South Brisbane, QLD, Australia
K. C. Nickels

¹⁶Mayo Clinic, Rochester, Minnesota, United States
R. Davis

¹⁷Neurology and Epilepsy Research Center, Orlando, Florida, United States
M. D. Lock

¹⁸Independent Statistical Consultant, Haiku, Hawaii, United States
D. Dai

¹⁹Syneos Health, Morrisville, North Carolina, United States
T. Minh

²⁰UCB, Morrisville, North Carolina, United States
R. Zhang Roper

²¹UCB, Slough, United Kingdom
A. Lothe

²²UCB, Colombes, France
M. Langlois

²²UCB, Colombes, France
S. Haas

²³UCB, Monheim am Rhein, Germany
A. Gil-Nagel

²⁴Hospital Ruber Internacional, Madrid, Spain

Abstract

Full Text

Background/Purpose: Lennox–Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy characterized by tonic seizures and other seizure types, intellectual impairment, and specific electroencephalogram findings. We describe the final long-term safety and effectiveness data from an open-label extension (OLE) study evaluating fenfluramine (FFA) in patients with LGS (NCT03355209).

Methods: After participating in an LGS randomized controlled trial (RCT), FFA was initiated at 0.2 mg/kg/day and then flexibly titrated to effectiveness/tolerability starting month 2. Outcomes reported include: incidence of treatment-emergent adverse events (TEAEs), median percentage change in seizures associated with a drop/fall, and change from baseline in caregiver Hospital Anxiety and Depression Scale (HADS) at month 12. Additional methods and statistical analyses have been described.[1]

Results: In total, 247 patients (mean age: 14.3 ± 7.6 years) were enrolled in the OLE; 174 (70.4%) were aged 2 to <18 years at RCT baseline. Median treatment duration, 364 days (range: 19–537). TEAEs reported in ≥10% of patients were: decreased appetite (16.2%), fatigue (13.4%), nasopharyngitis (12.6%), seizure (10.9%), and pyrexia (10.1%). Of 41 patients with ≥1 serious TEAE, 12 had ≥1 related to FFA. No cases of valvular heart disease or pulmonary arterial hypertension were observed. Median percentage change in frequency of seizures associated with a fall from month 2 to EOS (n = 240) was −31.1% (p < 0.0001); in pediatrics (n = 170), −27.6% (p = 0.0005). At FFA Mo12, significant improvement from baseline in caregiver anxiety on HADS was noted.

Conclusion: In this final analysis of an OLE study in patients with LGS, FFA was generally well tolerated with no new safety concerns identified. FFA was associated with a sustained reduction in seizures, confirming FFA as an important treatment option for patients with LGS.

References

References
1 Knupp, (2023), Epilepsia