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

    1   University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

  • A.-S. Schoonjans

    2   University Hospital Antwerp, Antwerp, Belgium

  • J. Sullivan

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

  • L. Lagae

    4   Member of the European Reference Network EpiCARE, Barcelona, Spain
    5   University of Leuven, Leuven, Belgium
    6   Leuven Childhood Epilepsy Center, Leuven, Belgium

  • R. Guerrini

    7   Meyer Children's Hospital IRCCS, Florence, Italy
    8   University of Florence, Florence, Italy

  • S. M. Zuberi

    9   Paediatric Neurosciences Research Group, School of Health & Wellbeing, University of Glasgow, Glasgow, United Kingdom
    10   Royal Hospital for Children, Glasgow, United Kingdom

  • R. Nabbout

    4   Member of the European Reference Network EpiCARE, Barcelona, Spain
    11   Reference Centre for Rare Epilepsies, Necker Enfants Malades Hospital, APHP, Paris, France
    12   Institut Imagine, U 1163, Paris, France
    13   Université Paris Cité, Paris, France

  • K. Riney

    14   The University of Queensland, St Lucia, QLD, Australia
    15   Queensland Children's Hospital, South Brisbane, QLD, Australia

  • K. C. Nickels

    16   Mayo Clinic, Rochester, Minnesota, United States

  • R. Davis

    17   Neurology and Epilepsy Research Center, Orlando, Florida, United States

  • M. D. Lock

    18   Independent Statistical Consultant, Haiku, Hawaii, United States

  • D. Dai

    19   Syneos Health, Morrisville, North Carolina, United States

  • T. Minh

    20   UCB, Morrisville, North Carolina, United States

  • R. Zhang Roper

    21   UCB, Slough, United Kingdom

  • A. Lothe

    22   UCB, Colombes, France

  • M. Langlois

    22   UCB, Colombes, France

  • S. Haas

    23   UCB, Monheim am Rhein, Germany

  • A. Gil-Nagel

    24   Hospital Ruber Internacional, Madrid, Spain
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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.



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Artikel online veröffentlicht:
26. September 2025

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