Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real‐world study

• Published in: Epilepsia (Copenhagen) Vol. 61; no. 11; pp. 2405 - 2414
• Main Authors: Specchio, Nicola, Pietrafusa, Nicola, Doccini, Viola, Trivisano, Marina, Darra, Francesca, Ragona, Francesca, Cossu, Alberto, Spolverato, Silvia, Battaglia, Domenica, Quintiliani, Michela, Luigia Gambardella, Maria, Rosati, Anna, Mei, Davide, Granata, Tiziana, Dalla Bernardina, Bernardo, Vigevano, Federico, Guerrini, Renzo
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2020
• Subjects: Adolescent; Adult; Anorexia - chemically induced; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Appetite loss; Child; Child, Preschool; childhood epilepsy; Clinical trials; Convulsions & seizures; convulsive seizures; Doppler effect; Dravet syndrome; Echocardiography; Epilepsies, Myoclonic - diagnostic imaging; Epilepsies, Myoclonic - drug therapy; Epilepsies, Myoclonic - physiopathology; Epilepsy; Female; Fenfluramine; Fenfluramine - administration & dosage; Fenfluramine - adverse effects; Follow-Up Studies; Genetic diversity; Heart; Humans; Male; Patients; Prospective Studies; SCN1A; Seizures; Seizures - diagnostic imaging; Seizures - drug therapy; Seizures - physiopathology; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - adverse effects; Treatment Outcome; Young Adult; childhood epilepsy; fenfluramine; Dravet syndrome; convulsive seizures; SCN1A
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.16690

Objective Dravet syndrome (DS) is a drug‐resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS. Methods DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add‐on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months. Results Fifty‐two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1‐13.9). Forty‐five (86.5%) patients completed the efficacy analysis. The median follow‐up was 9.0 months (IQR = 3.2‐9.5). At last follow‐up visit, there was a 77.4% median reduction in convulsive seizures. Thirty‐two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure‐free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA. Significance In this real‐world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.