FDA has approved, for the first time, a drug ingredient containing a purified drug substance derived from cannabis (Cannabis sativa) for the treatment of severe forms of epilepsy. The new drug, Epidiolex (GW Pharmaceuticals) comprises cannabidiol (CBD), a chemical compound in cannabis with potential health benefits, but does not contain tetrahydrocannabinol (THC), the compound in marijuana that causes intoxication. FDA says that this is the first time that it has approved a drug specifically targeting patients with Dravet syndrome, a rare form of epilepsy that begins in infancy.
Epidiolex is a liquid solution that is approved to treat not only Dravet syndrome, but also Lennox-Gastaut syndrome, another rare and severe form of epilepsy. Both genetic conditions are characterized by frequent seizures and reduced motor skills, including sitting and crawling. Patients with these conditions often require significant assistance with daily living. Epidiolex is now approved for patients two years old and above.
As a component of the cannabis plant, CBD is considered a Schedule I substance by FDA per the Controlled Substances Act. While initiatives like the proposed Hemp Farming Act of 2018, which would remove hemp from Schedule I of the Controlled Substances Act, would help to make use of cannabis-derived products more widespread, the legal status of CBD as an ingredient outside of the drug field, such as for dietary supplements, remains unclear. In warning letters FDA sent to several companies marketing CBD foods and dietary supplements in 2016, the agency said that hemp CBD is not considered a dietary ingredient because of existing investigational new drug (IND) applications filed by GW Pharma for the newly approved Epidiolex drug as well as another CBD drug, Sativex. Per regulations, if an ingredient was first studied under a drug IND, it is not permitted to be sold as a food or supplement ingredient.
In order to obtain FDA approval for this specific drug targeting two particular medical conditions, GW Research Ltd. evaluated Epidiolex’s efficacy and safety in three randomized, double-blind, placebo-controlled clinical trials. The trials included 516 patients with either Lennox-Gastaut syndrome or Dravet syndrome. In those studies, Epidiolex, taken with other medications, was shown to be effective in reducing the frequency of seizures when compared with placebo. Some of the side effects of treatment with Epidiolex included, among other, sleepiness, lethargy, diminished appetite, rashes, and infections.
Upon reviewing the research data for Epidiolex, FDA said it granted priority review designation for its application. FDA also granted fast-track designation for Epidiolex for Dravet syndrome. Finally, FDA granted orphan drug designation for Epidiolex for both Dravet and Lennox-Gastaut syndrome indications. Orphan drug designation gives special status to a drug or biological product to treat a rare disease or condition upon request of a sponsor.
“This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies. And, the FDA is committed to this kind of careful scientific research and drug development,” said FDA Commissioner Scott Gottlieb, MD, in a press release. “Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring marijuana-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes.”
Gottleib added that FDA plans to continue to support scientific efforts on the possible medical applications of marijuana-based ingredients, and to work with product developers to develop effective products. “At the same time,” he said, “we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”
In the press announcement, FDA stated that Epidiolex must be dispensed with a patient Medication Guide that details information about the drug’s uses and risks. “As is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks,” FDA said. Epidiolex may also cause liver injury, though generally mild.