Epidiolex, the cannabidiol oral solution, has recently been approved by the Food and Drug Administration in the United States for the treatment of seizures that are caused by Dravet or Lennox Gastaut Syndromes. These childhood onset epilepsy types are both severe and rare.
GW Pharmaceuticals in the UK, plus their US subsidiary, Greenwich Biosciences have announced the Food and Drug Administration’s recent approval of this politically and medically ground breaking prescription medicine. This is particularly noteworthy because it is the first cannabinoid plant-derived drug ever approved for use by the American public.
Dravet Syndrome and Lennox Gastaut Syndrome
Dravet Syndrome and Lennox Gastaut Syndrome develop in childhood. They are rare and very severe forms of epilepsy. They are notoriously resistant to existing treatments.
Patients generally require several different anti-seizure medications taken at once, and yet still remain resistant to these previously approved AEDs. The seizures continue, making the daily effect of the syndromes significant enough that there are high rates of early death.
Only approximately 50,000 patients in the US are currently suffering with the two illnesses the drug has FDA approval for. A similar number of patients exist in Europe, as well. Wired reports that that there is mounting evidence that Epidiolex would be a help for many other kinds of epilepsy and seizures.
In fact, evidence suggests that the CBD medicines are useful for a wide variety of neurological diseases like multiple sclerosis, Alzheimer’s, Parkinson’s, and some types of brain cancer.
Scott Gottlieb, the FDA Commissioner has stated his position in the Guardian UK as suggesting the approval will serve to remind the world that the advancement of sound development programs properly evaluating the active ingredients in marijuana will lead us to even more important medical therapies. He says that the FDA is now committed to this type of cautious drug development and scientific research.
Epidiolex should additionally be made available to doctors and patients in the UK and rest of Europe in mid-2019, assuming the European Medicines Agency follows with the expected approval early in the year.
Side Effects and Warnings
The FDA warns that patients using Valproate and Clobazam may have trouble with elevated ALT using Epidiolex. Clobazam use can increase the chance of transaminase elevations. Valproate has an even greater risk of elevated transaminase.
Since many patients are taking both, these interactions become significant. Up to 30 % of patients taking all 3 drugs have ALT elevations more than 3 X the ULN. In those taking only Valproate, the incidence dropped to 21 %. With only Clobazam the incidence dropped further to only 4 %, and the incidence has been tested as only 3 % in those only being treated with Epidiolex.
Physicians are instructed to discontinue the Valproate or Clobazam, or adjust the doses, as opposed to changing the treatment protocol with Epidiolex should the liver enzyme elevations be noted.
The Ingredients in Epidiolex
• The active ingredient in Epidiolex is cannabidiol.
• Epidiolex does not contain gluten (wheat, barley or rye).
• The inactive ingredients are listed as dehydrated alcohol, sesame seed oil, strawberry flavor, and sucralose.
The side effects most commonly noted in clinical trials were considered only if there was an incidence of at least 10 %, and if they were recorded as having a higher rate than the placebo.
Side effects are:
• Elevated transaminase liver enzymes that generally could cause a mild liver dysfunction
• Sleepiness, somnolence
• Decreased appetite
• Fatigue, malaise, asthenia
• Increased infections
• Insomnia, sleep disorder, poor quality sleep
Patients with Dravet Syndrome and Lennox Gastaut Syndrome were treated in both controlled and uncontrolled trials. 689 patients participated in the study in total. There were expanded access and compassionate use programs that provided additional information for the studies.
The placebo-controlled trial included 323 patients who received Epidiolex.
The treatment duration of the trials was up to and including 14 weeks. All of the patients in the study were already taking other types of AEDs to try to control their seizures.
Only 2.7 % of those participants in the controlled trials discontinued their use of Epidiolex as a result of an adverse reaction if they were taking the lower dose of 10 mg/ kg/ day. The rate was higher at an 11.8 % discontinuation rate for those who were taking the higher dose of 20 mg/ kg/ day. The most common reason for the discontinuation was the transaminase elevations.
An additional 3 % discontinued their use of Epidiolex at the higher dose of 20 mg /kg /day as they complained of sedation, somnolence, or lethargy. This side effect was not noted by any patients at the lower dose, nor for any of those patients who were receiving the placebo.
GW Pharmaceuticals remains committed to the development of new medicines designed for the treatment of those medication resistant, rare epilepsy conditions. They are specifically focusing on conditions where there remain limited or often, no treatment options that have won government approvals. Epidiolex is an excellent example of this ongoing commitment.