{
  "abstract": "Background Dravet syndrome (DS) is a rare, drug-resistant, developmental and epileptic encephalopathy characterized by frequent seizures and motor, behavioral, and cognitive impairments. Fenfluramine was evaluated in three pivotal phase 3 randomized-controlled studies ( NCT02682927, NCT02826863, NCT02926898) and is approved for the treatment of seizures associated with DS (US, EU, UK, Japan, among others) in patients ≥2 years old. The studies were pooled and stratified by baseline characteristics not originally reported.Methods Patients (2–18y) with DS were treated with placebo or fenfluramine (0.2 mg/kg/d or 0.7 mg/kg/d without stiripentol [0.2FFA, 0.7FFA], 0.4 mg/kg/d with stiripentol [0.4FFA]). Data were stratified by fenfluramine initiation age (<4y, ≥4y), severity (1–3, 4–6, and 7+ failed antiseizure medications [ASMs]), and genotype ( SCN1A+/-). Baseline characteristics, safety, median percentage change in monthly convulsive seizure frequency (MCSF), median longest interval of convulsive seizure-free days (SFDs), and Clinical Global Impression—Improvement (CGI-I) scores (caregiver/investigator) were assessed.Results Among 348 patients (0.2FFA, n=85; 0.4FFA, n=43; 0.7FFA, n=88; placebo, n=132), 83.7%-89.4% were ≥4y; 70.6%-81.4% had genotype SCN1A+. Failed ASM rates were generally high (4–6: 31.8%-48.8%; 7+: 34.8%-57.6% [no 0.4FFA-treated patients]). Treatment-emergent adverse events rates were similar across stratified groups. Fenfluramine treatment was associated with greater decrease in MCSF, increase in longest interval of SFDs, and higher CGI-I scores versus placebo, regardless of stratification.Conclusions Fenfluramine is associated with improved outcomes relative to placebo, regardless of age, severity, or genotype. Analyses of stratified groups in larger populations may provide a better understanding of the benefits seen with various DS subpopulations and synergies with concomitant medications.",
  "authors": [
    {
      "affiliations": [
        "Member of the European Reference Network EpiCARE; Reference Centre for Rare Epilepsies, Hôpital Universitaire Neckers-Enfants Malades, APHP, Institut Imagine, INSERM 1163, Université Paris Cité, Paris, France"
      ],
      "name": "Rima Nabbout"
    },
    {
      "affiliations": [
        "Department of Neurology and Pediatrics, University of California San Francisco Weill Institute for Neurosciences, Benioff Children’s Hospital, San Francisco, California, USA"
      ],
      "name": "Joseph Sullivan"
    },
    {
      "affiliations": [
        "Member of the European Reference Network EpiCARE, AP-HP, Reference Center for Rare Epilepsies, Hôpital Universitaire Robert Debré, Paris, France",
        "Institut Hospitalo-Universitaire Robert-Debré du Cerveau de l’Enfant, Paris, France",
        "Université Paris-Cité, INSERM NeuroDiderot, Paris, France",
        "Institut Universitaire de France (IUF), Paris, France"
      ],
      "name": "Stéphane Auvin"
    },
    {
      "affiliations": [
        "UCL NIHR BRC Great Ormond Street Institute of Child Health, Great Ormond Street Hospital, London, UK"
      ],
      "name": "Helen J Cross"
    },
    {
      "affiliations": [
        "Departments of Neurology and Neurosurgery, Comprehensive Epilepsy Center, NYU Langone Medical Center, New York City, New York, USA"
      ],
      "name": "Orrin Devinsky"
    },
    {
      "affiliations": [
        "Department of Neurology, Epilepsy Program, Hospital Ruber Internacional, Madrid, Spain"
      ],
      "name": "Antonio Gil-Nagel"
    },
    {
      "affiliations": [
        "Meyer Children’s Hospital IRCCS and University of Florence, Florence, Italy"
      ],
      "name": "Renzo Guerrini"
    },
    {
      "affiliations": [
        "University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"
      ],
      "name": "Kelly G Knupp"
    },
    {
      "affiliations": [
        "Jane and John Institute for Mind Health, Cook Children’s Medical Center, Fort Worth, Texas, USA"
      ],
      "name": "Scott M Perry"
    },
    {
      "affiliations": [
        "Pediatric Neurology Unit, Clínica Universidad de Navarra, Av. de Pío XII, 36, 31008, Pamplona, Spain"
      ],
      "name": "Rocio Sanchez-Carpintero"
    },
    {
      "affiliations": [
        "University of Melbourne, Austin Hospital and Royal Children’s Hospital, Florey and Murdoch Children’s Research Institutes, Melbourne, VIC, Australia"
      ],
      "name": "Ingrid Scheffer"
    },
    {
      "affiliations": [
        "Member of the European Reference Network EpiCARE; Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesú Children’s Hospital, IRCCS, Rome, Italy",
        "University Hospitals KU Leuven, Leuven, Belgium"
      ],
      "name": "Nicola Specchio"
    },
    {
      "affiliations": [
        "Goethe University Frankfurt, Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany"
      ],
      "name": "Adam Strzelczyk"
    },
    {
      "affiliations": [
        "University of Tennessee Health Science Center and Le Bonheur Children’s Hospital, Memphis, Tennessee, USA"
      ],
      "name": "James Wheless"
    },
    {
      "affiliations": [
        "Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Elaine C Wirrell"
    },
    {
      "affiliations": [
        "UCB, Melbourne, VIC, Australia",
        "Department of Medicine, St. Vincent’s Hospital, University of Melbourne, Melbourne, VIC, Australia"
      ],
      "name": "Jeremy Welton"
    },
    {
      "affiliations": [
        "UCB, Morrisville, North Carolina, USA"
      ],
      "name": "Diego Morita"
    },
    {
      "affiliations": [
        "UCB, Colombes, France"
      ],
      "name": "Mélanie Langlois"
    },
    {
      "affiliations": [
        "UCB, Smyrna, Georgia, USA"
      ],
      "name": "Patrick Healy"
    },
    {
      "affiliations": [
        "UCB, Colombes, France"
      ],
      "name": "Amélie Lothe"
    },
    {
      "affiliations": [
        "Member of the European Reference Network EpiCARE, Department of Development and Regeneration, University of Leuven, Leuven, Belgium"
      ],
      "name": "Lieven Lagae"
    }
  ],
  "title": "3457 A stratified analysis of efficacy and safety of fenfluramine in patients with dravet syndrome",
  "uid": "b67cf285-da1b-512e-8f4a-7b9abe29ca8d"
}