Dravet syndrome is a rare and severe type of epilepsy that appears in infancy.
Based on previous medical experiences, the current standard of care for Dravet syndrome includes valproate (Epilim, Depakote), topiramate (Topamax), clobazam (Frisium), and stiripentol (Diacomit). Some patients may require a combination of these anti-epileptic medications to control their seizures while others may not respond to any of them.
Several lines of research are ongoing to develop new therapies for Dravet syndrome and to more effectively control seizures.
ZX008 is an investigational therapy being developed by Zogenix for the treatment of Dravet syndrome. It is a liquid solution of low dose fenfluramine hydrochloride, a compound derived from the stimulant amphetamine.
The anti-epileptic property of ZX008 is via the stimulation of serotonin release in the brain.
A study published in 2012 showed that ZX008 plus valproate resulted in significantly fewer seizures in Dravet syndrome patients. The therapy prevented seizures in seven of the ten patients treated for as long as one year (when they were still taking the medicine). Following five years of treatment, three patients remained seizure-free, and researchers observed no major heart or lung problems due to fenfluramine.
Four Phase 3 clinical trials (NCT02926898, NCT02682927, NCT02826863, and NCT02823145) testing ZX008 are currently ongoing with the third still recruiting and the fourth enrolling by invitation. Results from the first study showed that ZX008 significantly decreased seizure frequency and improved the overall condition of patients with Dravet syndrome.
The U.S. Food and Drug Administration granted fast track designation to ZX008 in 2016. The therapy also received orphan drug status from both the FDA and the European Medicines Agency. In February, the FDA accepted ZX008 as a breakthrough therapy, which will speed up its review process.
Epidiolex (cannabidiol, GWP42003-P)
A number of clinical trials were engineered to evaluate the benefits of Epidiolex for Dravet syndrome patients. Positive results from these studies led to Epidiolex receiving orphan drug and fast track designations from the FDA and the EMA for the treatment of Dravet syndrome.
The first of these studies, the GWPCARE1 trial, was designed in two parts: Part A (NCT02091206) identified a safe dose of Epidiolex, and Part B (NCT02091375) assessed its effects on seizures caused by Dravet syndrome.
GWPCARE1 Part A was a Phase 2 study where 34 patients were randomly assigned to four groups and treated with either three doses of Epidiolex (5, 10, or 20 mg/kg daily), or placebo. The results showed that 20 mg/kg of Epidiolex daily was safe and well tolerated without any negative interactions with other anti-epileptic medications.
Following this safety assessment, GWPCARE1 Part B was initiated. In this randomized Phase 3 study, 120 children with Dravet syndrome younger than 18 were treated with Epidiolex or placebo for 14 weeks. Results showed that seizure frequency in patients taking Epidiolex decreased approximately by half, and three of the 61 patients who were taking Epidiolex became seizure-free during the course of the treatment. The most common side effects of Epidiolex were vomiting, fatigue, drowsiness, fever, upper respiratory tract infection, diarrhea, and decreased appetite.
A Phase 3 clinical trial (NCT02224703) called GWPCARE2, which is the extension study of GWPCARE1, is currently recruiting Dravet syndrome patients across the U.S. and the Netherlands to compare the efficiency and safety of two different doses of Epidiolex.
Another Phase 3 trial (NCT02224573) called GWPCARE5 is currently enrolling participants by invitation only who have successfully completed GWPCARE1 or GWPCARE2.
Research is ongoing to develop different approaches for the treatment of Dravet syndrome such as gene therapy, the discovery of new therapeutic compounds, and the identification of new genes that may be involved in disease progression, so they can be targeted in future therapies.
Although these studies are in very early stages, they are important to better understand Dravet syndrome and to better treat the disease in the future.
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