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. 2025 Apr;66(4):1110-1118.
doi: 10.1111/epi.18241. Epub 2024 Dec 30.

Fenfluramine treatment for Dravet syndrome: Long term real-world analysis demonstrates safety and reduced health care burden

Alessandra Boncristiano  1 , Simona Balestrini  1   2 , Viola Doccini  1 , Nicola Specchio  3   4 , Nicola Pietrafusa  3 , Marina Trivisano  3 , Francesca Darra  5   6 , Alberto Cossu  6 , Domenica Battaglia  7 , Michela Quintiliani  7 , M Luigia Gambardella  7 , Eliana Parente  8 , Rita Monni  9 , Sara Matricardi  10   11 , Carla Marini  11 , Francesca Ragona  12 , Tiziana Granata  12 , Pasquale Striano  13   14 , Antonella Riva  13   14 , Renzo Guerrini  1   2
Affiliations

Fenfluramine treatment for Dravet syndrome: Long term real-world analysis demonstrates safety and reduced health care burden

Alessandra Boncristiano et al. Epilepsia. 2025 Apr.

Abstract

Objective: Fenfluramine (FFA), stiripentol (STP), and cannabidiol (CBD) are approved add-on therapies for seizures in Dravet syndrome (DS). We report on the long-term safety and health care resource utilization (HCRU) of patients with DS treated with FFA under an expanded access program (EAP).

Methods: A cohort of 124 patients received FFA for a median of 2.8 years (34.4 months). We compared data on safety and HCRU during FFA treatment with those from a same pre-treatment period. Echocardiography was conducted every 6 months. Information collected included gender, age, and auxological parameters (height, weight, and body mass index [BMI]) at the start (T0) and follow-up (T1); FFA treatment details (start, withdrawal, dosage); adverse events (AEs); and HCRU data including hospital admissions, status epilepticus (SE) episodes, and rescue medication use. We grouped patients by weight: ≤37.4 kg (n = 68, 54.8%) and ≥37.5 kg (n = 56; 45.1%), with FFA dosing adjusted accordingly. Statistical analyses included paired t test, Wilcoxon signed-rank test, Kaplan-Meier analysis, and Bonferroni correction to adjust for multiple testing.

Results: Mean age was 47 months at clinical diagnosis and 81 months at T0. The last follow-up average FFA dose was .5 mg/kg/day, with a median of .4 mg/kg/day. FFA led to a 9.5% reduction in prior treatment load. At last follow-up, 118 of 124 (91.5%) remained on FFA. Rescue medication use decreased significantly from 4.5 to 1, hospitalizations from 1 to 0, and SE episodes from 0-240 to 0-180 (p < .001 for all). Seizure freedom was achieved in 9 of 118 patients (7.6%). AEs occurred in 39 of 124 patients (31.5%), with no cardiac issues or deaths. There was an overall mean reduction in BMI, with no statistical significance, and never requiring FFA withdrawal.

Significance: FFA is well tolerated, without cardiac toxicity, and reduces treatment load and HCRU, suggesting improved patient management. BMI reduction in young children highlights the need for growth and nutritional monitoring.

Keywords: SCN1A; antiseizure; encephalopathy; epilepsy; medication; pharmacoeconomics.

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Conflict of interest statement

Alessandra Boncristiano has received speaker honoraria from UCB. Simona Balestrini has served on scientific advisory boards for Biocodex and Longboard Pharmaceuticals; and has received speaker honoraria from Angelini, Biocodex, Eisai, Lusofarmaco, and Jazz Pharma. Viola Doccini has served as an investigator for Biocodex. Nicola Specchio has served on scientific advisory boards for GW Pharma, BioMarin, Arvelle, Marinus, and Takeda; has received speaker honoraria from Eisai, Biomarin, Livanova, Sanofi, Jazz Pharmaceutical, UCB, and Takeda; and has served as an investigator for Zogenix, Marinus, Biomarin, UCB, and Roche. Nicola Pietrafusa has received speaker honoraria from Angelini, Zogenix, and UCB. Marina Trivisano has served on scientific advisory boards for Biomarin and Biocodex; she has received speaker honoraria from Biomarin and Orion Pharma. Francesca Darra has served on scientific advisory boards for Zogenix, Biocodex, Angelini, UCB, and Ethypharm; and has received speaker honoraria from Biocodex, GW‐Jazz, and UCB. Alberto Cossu has received speaker honoraria from UCB. Domenica Immacolata Battaglia has served on scientific advisory boards for Biocodex, UCB, and Ethypharm. Eliana Parente has received speaker honoraria from UCB. Rita Monni has served on scientific advisory boards for UCB Pharmaceuticals and has received speaker honoraria from UCB. Sara Matricardi has served on scientific advisory boards for Zogenix, UCB, and Ethypharm; and has received speaker honoraria from Biocodex, Jazz Pharmaceuticals, Eisai, and UCB. Carla Marini has served on scientific advisory boards for UCB and Ethypharm; and has received speaker honoraria from Jazz Pharmaceuticals, Eisai, and UCB. Francesca Ragona has served on scientific advisory boards for Biocodex, Zogenix, and GW‐Jazz; and has received speaker honoraria from UCB and GW‐Jazz. Tiziana Granata has served on scientific advisory boards for Ethypharm. Pasquale Striano has served on scientific advisory boards for Zogenix, Biocodex, GW‐Jazz, Angelini, Takeda, UCB, and Ethypharm; has received speaker honoraria and funding for travel from Zogenix, Biocodex, GW‐Jazz, Angelini, Takeda, and UCB; and has served as an investigator for Zogenix, Biocodex, and UCB. Antonella Riva has served on scientific advisory boards for Biocodex, UCB, Jazz Pharmaceutical, and PTC therapeutics; and has received travel grants from Jazz Pharmaceuticals. Renzo Guerrini has served on scientific advisory boards for Zogenix, Biocodex, GW‐Jazz, Angelini, Takeda, Rapport Therapeutics, SK Life Science Inc., Stoke Therapeutics, UCB, and Ethypharm; has received speaker honoraria and funding for travel from Zogenix, Biocodex, GW‐Jazz, Angelini, Takeda, Rapport Therapeutics, Novartis, SK Life Science Inc., Stoke Therapeutics, UCB, Marinus, and GRIN Therapeutics; and has served as an investigator for Zogenix, Biocodex, UCB, GRIN Therapeutics, SK Life Science Inc., TEVA, Marinus, Lundbeck, and The Loulou Foundation.

Figures

FIGURE 1
FIGURE 1
Retention of fenfluramine over time (Kaplan–Meier analysis). Horizontal axis, follow‐up time in months; vertical axis, proportion of patients receiving fenfluramine treatment.
See this image and copyright information in PMC

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