Epidiolex (formerly, GWP42003-P) is an oral cannabidiol solution developed by GW Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) to treat seizures in people with Dravet syndrome and Lennox-Gastaut syndrome starting at age 2.
Under the brand name Epidyolex, it is also approved in the EU to treat patients with Dravet syndrome or Lennox-Gastaut syndrome over age 2, in conjunction with clobazam (an anti-epileptic medication).
How does Epidiolex work?
Epidiolex is a plant-derived cannabidiol, a non-psychoactive marijuana extract, meaning it does not have the mind-altering effects that are characteristic of delta (9)-tetrahydrocannabinol (THC), the main psychoactive component of marijuana that gets people “high.”
While marijuana derivatives have been used to treat epilepsy since the late 19th century, researchers still do not fully understand how cannabidiol works to treat epilepsy. They hypothesize that it may be due to its ability to interact with many other non-cannabinoid receptors in the brain. (The brain has a natural endocannabinoid system — which has an important regulatory role in the related of hormones related to reproductive functions and response to stress — with cannabinoid receptors that can respond to CBD and THC.)
Epidiolex in clinical trials
An open-label, Phase 1 clinical trial (NCT02286986) compared the safety and tolerability of increasing doses of Epidiolex given to patients, ages 2 to 19, with drug-resistant epilepsy. Researchers also aimed to determine changes in the number of seizures experienced during a year. The trial was completed, but the results have not been published.
Results from a Phase 3 clinical trial (NCT02091375) conducted at 23 centers in the U.S. and Europe found that 120 children and young adults, ages 2 to 19, who were given 20 mg per kilogram bodyweight of Epidiolex for three-and-a-half months had half the average number of convulsive seizures per month compared to the number they experienced before treatment (5.9 vs. 12.4).
Five percent of those receiving Epidiolex were seizure-free for the duration of the study. However, Epidiolex did not reduce the number of non-convulsive seizures. A majority of caregivers, 62%, reported noticing in Epidiolex-treated patients an improvement of at least one category in the caregiver global impression (CGI) scale, as did 34% of caregivers of those in the placebo group.
The most common side effects of treatment were fatigue, fever, vomiting, diarrhea, sleepiness, and abnormal liver enzyme test results, recorded in 93% of patients taking Epidiolex. A majority of these (89 percent) were of mild-to-moderate severity. The findings from this trial were published in The New England Journal of Medicine.
Another Phase 3 clinical trial (NCT02224703) that began in 2015 assessed the safety and effectiveness of Epidiolex in children and young adults with Dravet syndrome. The trial compared a high dose (67 patients) and low dose (67 patients) of Epidiolex to placebo (65 patients), and measured changes in the number of epileptic (convulsive) seizures from the study’s start until after 14 weeks of treatment. The trial took place at clinical sites in the U.S. and in the Netherlands. Trial results were presented at the 2019 American Academy of Neurology (AAN) Annual Meeting. Of the 199 children, a 46% of those in the high-dose group and and 49% in the low-dose group saw a reduction in convulsive seizures, compared to 27% of patients on placebo.
The incidence of adverse events was similar across all groups, at around 90%. The most common were decreased appetite, diarrhea, excessive sleepiness, fever, and fatigue.
An open-label, Phase 3 extension trial (NCT02224573) is currently underway. It aims to record side effects, improvements in seizure symptoms, and overall improvements in quality of life in patients who were in previous clinical trials of Epidiolex. This study is expected to be completed in June 2020.
Epidiolex had the largest expanded access program (also known as a compassionate use program) in epilepsy, a program that allows patients with potentially life-threatening conditions to gain access to treatments not available outside of clinical trials. Through this program, more than 1,100 patients were able to receive Epidiolex treatment. The medication was provided by Greenwich Biosciences, a subsidiary of GW Pharmaceuticals.
Last updated: Oct. 26, 2019
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