The Food and Drug Administration (FDA) has approved fenfluramine (Fintepla; Zogenix, Emeryville, CA), oral solution for treatment of seizures associated with Dravet syndrome (DS) in individuals age 2 years or more. Fenfluramine will be launched through a restricted distribution program, called the fenfluramine risk evaluation and mitigation strategy (REMS) program and is expected to be available through Zogenix’s specialty pharmacy partner by the end of July.
The FDA’s approval of fenfluramine in DS was based on data from 2 randomized, double-blinded, placebo-controlled phase 3 clinical trials, published in The Lancet and JAMA Neurology, and safety data from an open-label extension trial in which many individuals received fenfluramine for up to 3 years. When added to existing treatment regimens, fenfluramine significantly reduced the monthly convulsive seizure frequency compared to placebo in study patients whose seizures were not adequately controlled on 1 or more antiepileptic drugs. Most study participants responded to treatment with fenfluramine within 3 to 4 weeks and effects remained consistent over the treatment period.
In study 1504 phase 3 study (NCT02926898), participants with DS treated with stiripentol but still having a high number of convulsive seizures had a significant and clinically meaningful (> 50%) reduction in monthly convulsive seizure frequency (MCSF). In study 1504, the median longest seizure-free interval was 22 days (3.0-105.0) with fenfluramine and 13 days (1.0-40.0) with placebo (P=.004). Increasing days without seizures is likely to improve an individual’s ability to participate in other therapies and activities that can improve quality of life for people with DS. In some clinical studies of fenfluramine, seizure reduction with fenfluramine treatment correlated with improved cognitive gains.
The most common adverse reactions (incidence at least 10% and greater than placebo) were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus.
Fenfluramine will be available to certified prescribers in the US in July. Zogenix is launching a comprehensive support service that will provide ongoing product assistance to patients, caregivers, and their medical teams.