SILVER SPRING, Md. -- Pharmaceutical-grade cannabidiol (Epidiolex) was recommended for FDA approval as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, via a unanimous FDA committee vote Thursday.
The FDA is now expected to decide the medication's fate by late June, according to Justin Gover, CEO of , which manufactures Epidiolex. If approved, Epidiolex would become the first medication derived from the cannabis plant allowed in the U.S.
"We are reviewing this application on an expedited timeline," an FDA representative said after the committee vote, "working to accelerate this process as much as we can."
Advocates celebrated the committee vote.
"Despite significant therapeutic advances in the last few years," the Epilepsy Foundation said in a statement issued shortly after the meeting, "there is a great unmet need in the epilepsy community, as more than a third of people living with epilepsy do not have seizure control, and many more live with significant side effects that impact cognitive ability, mood, and memory ... Epidiolex represents hope for the many individuals living with intractable seizures and rare epilepsies."
Several epilepsy patients and family members spoke during the meeting's public hearing Thursday, advocating for Epidiolex as well as cannabidiol (CBD) more broadly to prevent and treat seizures. "Epidiolex is by far the best medication she has taken, and it has the fewest side effects," one woman said of her daughter, who tried six different drugs before settling on Epidiolex 4 years ago. "Hundreds of thousands of kids could benefit."
Members of the FDA's Peripheral and Central Nervous System Drugs Advisory Committee clearly agreed, voting 13-0 (without anyone abstaining) in favor of approving Epidiolex.
"There's obviously a real need," said Harriet de Wit, PhD, a psychiatry and behavioral neuroscience professor at the University of Chicago.
Richard P. Hoffman, PharmD, the committee's acting consumer representative, cited the three "high-quality" studies with large sample sizes conducted to test the medication that committee members examined. The adverse events revealed by the studies appear to be "very manageable with labeling and education," said Hoffman, a pharmacist and medical writer in Florida.
"This is clearly a breakthrough drug," said John Mendelson, MD, a research scientist with Friends Research Institute and chief medical officer with Ria Health in San Francisco. But, he added, "the question will be phase 4 [trial] monitoring."
Epidiolex will also need further study to determine proper dosing regimens, experts said at the meeting. GW Pharmaceuticals suggests administering the agent orally in doses of 10 (including 750 mg of CBD) and 20 (1500 mg) mg/kg/day.
The committee, chaired by Caleb Alexander, MD, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness, at Bloomberg School of Public Health, Baltimore, voted on only one question Thursday: whether the benefit-risk profile of the cannabis derivative is favorable to treat seizures associated with LGS and Dravet syndrome in people age 2 and older.
Epidiolex's application and safety data encompassed treatment of about 1,500 patients, according to GW Pharmaceuticals.
The risk-benefit profile established by the three trials "appears to support approval," according to an FDA review issued to the committee before the meeting. The trials demonstrated clinically meaningful and statistically significant reductions in seizure frequency, and the results "provide substantial evidence" of cannabidiol's effectiveness in treating LGS and Dravet syndrome seizures.
Regarding possible CBD risks, an FDA controlled-substances staff report concluded that CBD has negligible abuse potential. In addition the FDA review reported: "Although the risk of liver injury has the potential to be serious, the observed risk can be appropriately managed with inclusion of relevant language in labeling, education of prescribers regarding the risk of transaminase elevation and need for monitoring of liver enzyme levels, and further characterization of the risk in the post-market setting," according to the review.
LGS and Dravet syndrome are rare, severe, refractory epilepsy syndromes that emerge early in childhood. Both are linked to higher mortality rates, primarily due to status epilepticus and sudden unexpected death in epilepsy patients. CBD, a cannabinoid found in cannabis, is structurally unrelated to other anti-seizure medications and currently is a Schedule I drug. Its anticonvulsant mechanism is unknown but does not appear to involve cannabinoid receptors.
Epidiolex features a solution of 100 mg/ml of CBD dissolved in sesame oil, ethanol, sweetener, and a flavoring agent, according to the review. The medication is harvested from cannabis plants specifically bred for medical purposes, with high CBD concentration, according to a GW Pharmaceuticals report.
The committee vote Thursday not only boosts Epidiolex's chances of becoming a viable medical treatment, but also provides momentum for using CBD and other cannabinoids in additional pharmaceutical forms. CBD is one of dozens of cannabinoids found in cannabis.
The FDA has previously approved synthetic cannabis medications, which more closely resemble tetrahydrocannabinol (THC), but nothing plant-derived nor anything featuring CBD. Sativex, which incorporates both THC and CBD, has been approved for medical use outside the U.S.
Last year the National Academies Health and Medicine division declared that "conclusive or substantial" evidence exists to use non-synthetic cannabis to treat multiple sclerosis spasticity symptoms, cancer-related nausea and vomiting, and chronic pain in adults.
GW Pharmaceuticals alone is studying cannabinoids to treat other forms of epilepsy, autism, cancer, and multiple sclerosis. (Most studies are in early stages, Gover cautioned.) "There's real potential," Gover said. Thursday's vote validates that "we have demonstrated that a cannabinoid has the potential to be formally assessed in a scientific way" and for a regulatory body to take a cannabinoid seriously as a medication.
GW Pharmaceuticals has also received Orphan Designation for Epidiolex from the regulatory body European Medicines Agency to treat LGS, Dravet Syndrome, and West syndrome; Gover said he expects a decision by early next year.
"This is a hugely important day for us as a company and for me personally," he said.
The FDA review drew largely from two pivotal 14-week, multicenter, randomized, double-blind, placebo-controlled trials in patients with LGS, and one similar study of Dravet syndrome patients.
The FDA is not obliged to follow advisory committee recommendations but usually does.