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

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.