Zogenix announced JAMA Neurology, has published the results of Zogenix’s Phase 3 Study 1504 which evaluated Fintepla (ZX008, fenfluramine oral solution) in Dravet syndrome patients whose antiepileptic drug treatment regimens included stiripentol but who were still experiencing a high number of convulsive seizures. The study demonstrated that adding Fintepla to these patients’ treatment regimens led to a significant and clinically meaningful (> 50%) reduction in monthly convulsive seizure frequency (MCSF).
Study 1504 was an international, double-blind, placebo-controlled study of 87 Dravet syndrome patients age 2-19 taking background anti-epileptic drug regimens that included stiripentol. Eligible patients in the trial were experiencing seizures that were poorly controlled with their current anti-seizure medications consisting of stiripentol plus clobazam and/or valproic acid. After a 6-week period to establish baseline seizure frequency, patients were randomized to receive Fintepla starting at a dose of 0.2 mg/kg/day, twice-daily with gradual blinded titration over a 3 week period to 0.4 mg/kg/d (maximum of 17 mg per day) over 3 weeks. Patients maintained their regimen for an additional 12 weeks at a stable dose, then either continued treatment in an open-label extension study or discontinued treatment.
The study met its primary efficacy endpoint and all key secondary endpoints. Patients treated with Fintepla achieved a 54% greater reduction in mean MCSF than those receiving the placebo. Additionally, 54% of patients treated with Fintepla experienced a clinically meaningful (>50%) reduction in MCSF versus 5% with placebo. Profound seizure reduction (>75% reduction in MCSF) was experienced by 35% of Fintepla-treated patients compared to 2% with placebo. The median longest seizure-free interval was 22 days with Fintepla and 13 days with placebo. The most common adverse events were decreased appetite, fatigue, diarrhea and pyrexia.
A New Drug Application (NDA) for FIntepla for Dravet syndrome has been accepted for review by the U.S. Food & Drug Administration. A Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency.
About Fintepla (ZX008, fenfluramine oral solution)
Fintepla is a low-dose oral solution of fenfluramine hydrochloride and is an amphetamine derivative.
About Dravat Syndrome
Dravet syndrome, previously called severe myoclonic epilepsy of infancy (SMEI), is an epilepsy syndrome that begins in infancy or early childhood and can include a spectrum of symptoms ranging from mild to severe. Children with Dravet syndrome initially show focal (confined to one area) or generalized (throughout the brain) convulsive seizures that start before 15 months of age (often before age one). These initial seizures are often prolonged and involve half of the body, with subsequent seizures that may switch to the other side of the body. Other seizure types emerge after 12 months of age. In at least 80 percent of cases, Dravet syndrome is caused by mutations in the SCN1A gene.