Fenfluramine HCL Substantially Reduces Seizure Frequency in Children
All participants enrolled in this open-label extension study had previously completed a phase 3 clinical trial of fenfluramine.
|The following article is part of conference coverage from the American Epilepsy Society's Annual Meeting in New Orleans, LA. The Neurology Advisor's staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2018.|
NEW ORLEANS — Compared with placebo, fenfluramine hydrochloride provides substantial and clinically meaningful reductions in the frequency of convulsive seizures in pediatric patients with Dravet syndrome, according to research presented at the 72nd Annual Meeting of the American Epilepsy Society, held November 30-December 4, 2018.
The results were from a preliminary interim analysis of a long-term, open-label extension study (ClinicalTrials.gov Identifier: NCT02823145) of fenfluramine vs placebo in children and young adults ages 2 to 18 with Dravet syndrome.
All participants (N=232; 55.2% male; mean±SD age=9.1±4.7 years) enrolled in the open-label extension study had previously completed a phase 3 clinical trial of fenfluramine, and all of them initiated fenfluramine at 0.2 mg/kg/d at the start of the study, regardless of what dose they had received in the clinical trial. This dose could be titrated up by 0.2 mg/kg/d up to a 0.8 mg/kg/d maximum after 4 weeks. Efficacy was assessed monthly in the first 3 months, and thereafter in 3-month intervals.
Overall, 22 of the 232 participants discontinued fenfluramine: 16 due to lack of efficacy, 2 due to participant withdrawal, 1 due to an adverse event, 1 due to physician decision, 1 due to withdrawal by caregiver, and 1 by sudden unexplained death in epilepsy. Median treatment duration was 256 days (range, 58-634 days).
The median percentage reduction in convulsive seizure frequency per month during the entire open-label extension study treatment period was 66.8%, compared with the baseline frequency in the Phase 3 clinical trials.
The clinically meaningful reduction in seizure frequency that was noted at month 1 of the open-label extension study continued over time, with 64.4% of participants showing a ≥50% reduction in frequency during the entire observation period, and 41.2% showing a ≥75% reduction in frequency. After 12 months, 77.8% of investigators and 70.4% of caregivers rated participants as "much" or "very much" improved.
Investigators concluded that fenfluramine "continues to provide clinically meaningful and substantial reductions in convulsive seizure frequency over extended periods of time; while being generally well tolerated. [Fenfluramine] represents a novel, highly effective antiepileptic treatment option for patients with Dravet syndrome."
Disclosures: Study funding was provided by Zogenix, Inc.
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Lagae L, Sullivan J, Nabbout R, et al. Fenfluramine HCL (Fintepla®) provides long-term clinically meaningful reduction in seizure frequency: results of an open-label extension study. Presented at: 72nd Annual Meeting of the American Epilepsy Society; November 30-December 4, 2018; New Orleans, LA. Poster 3.463.