An examination of the efficacy and safety of fenfluramine in adults, children, and adolescents with Dravet syndrome in a real‐world practice setting: A report from the Fenfluramine European Early Access Program

• Published in: Epilepsia open Vol. 7; no. 4; pp. 578 - 587
• Main Authors: Guerrini, Renzo, Specchio, Nicola, Aledo‐Serrano, Ángel, Pringsheim, Milka, Darra, Francesca, Mayer, Thomas, Gil‐Nagel, Antonio, Polster, Tilman, Zuberi, Sameer M., Lothe, Amélie, Gammaitoni, Arnold, Strzelczyk, Adam
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-12-2022; Wiley
• Subjects: Adolescent; Adult; Age groups; Anticonvulsants - therapeutic use; Cardiovascular disease; Caregivers; Child; clinical practice; Clinical trials; Comorbidity; Convulsions & seizures; Dravet syndrome; Epilepsies, Myoclonic - drug therapy; Executive function; fenfluramine; Fenfluramine - adverse effects; Humans; Hypertension; Participation; Patients; Pulmonary arteries; refractory epilepsy; seizures; Seizures - drug therapy; Treatment Outcome; Veins & arteries; clinical practice; seizures; refractory epilepsy; fenfluramine; Dravet syndrome
• ISSN: 2470-9239; 2470-9239
• DOI: 10.1002/epi4.12624

Objective
To examine the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) in three age groups: <6, 6‐17, and ≥18 years old, treated in a real‐world setting.
Methods
Patients with DS were treated with fenfluramine in the European Union Early Access Program (EAP). Following a 28‐day baseline period to establish the pretreatment monthly convulsive seizure frequency (MCSF), fenfluramine was started at a dose chosen by the treating physician and gradually titrated based on efficacy and tolerability up to a maximum of 0.7 mg/kg/day. Seizure incidence was recorded in a written diary, and adverse events (AEs) were reported at each patient visit. Cardiovascular safety was assessed by transthoracic echocardiography before treatment started and at least every 6 months thereafter.
Results
A total of 149 patients have enrolled in the EAP and 63 were <6 years old, 62 were 6‐17 years old, and 24 were ≥18 years old. After 3 months of treatment 62%, 53%, and 50% of patients demonstrated ≥75% reduction in MCSF in the <6, 6‐17, and ≥18‐year‐old groups, respectively. This pattern of response was sustained through 12 months of treatment with 55%, 46%, and 80% of the <6, 6‐17, and ≥18‐year‐old groups, respectively, experiencing a ≥75% reduction in MCSF. Most common AEs were loss of appetite (21%) and somnolence (16%). No valvular heart disease or pulmonary artery hypertension was observed.
Significance
The magnitude, consistency, and durability of the response to add‐on fenfluramine is consistent across age groups in patients with Dravet syndrome.