The FDA will come to a conclusion on whether to approve Epidiolex in late June and if approved, this will be the first cannabis-based product to become FDA approved.
Orrin Devinsky, MD
A new large-scale trial found that an oral formulation of cannabidiol, Epidiolex, significantly resulted in greater reductions in the frequency of drop seizures in adult and children patients with Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy.
In the phase 3 trial, researchers compared 2 doses of cannabidiol to placebo and reported a 41.9% reduction in drop seizures in patients prescribed a 20 mg/kg/day cannabidiol regimen, a 37.2% reduction in those on a 10 mg/kg/day cannabidiol regimen and a 17.2% reduction in the group given placebo (P = 0.005 for the 20-mg cannabidiol group versus placebo group, and P = 0.002 for the 10-mg cannabidiol group vs. placebo group).
“These results provide important and novel information about the efficacy and safety of 2 doses of Epidiolex,” Orrin Devinsky, MD, professor of neurology, neurosurgery and psychiatry, NYU School of Medicine, and director of NYU Langone’s comprehensive epilepsy center, told MD Magazine. “This is critical information for us to better care for patients when the medication is available for widespread use.”
In the double-blind, placebo-controlled trial conducted at 30 clinical centers, researchers enrolled 225 patients with Lennox-Gastaut syndrome, between the ages of 2—55 years old, who had 2 or more drop seizures per week during a 28-day baseline period.
Participants were randomly assigned to receive cannabidiol oral solution at either 20 mg per kilogram of body weight (76 patients) or 10 mg per kilogram (73 patients) or a matching placebo (76 patients). All medications were administered in 2 equally divided doses daily, for 14 weeks.
The number of seizures were monitored beginning 4 weeks prior to the study for baseline assessment, then tracked through the 14-week study period, and afterward for a 4-week safety follow-up.
During the 28-day baseline period, the median number of drop seizures combined from all trial groups was 85.
Researchers concluded that the 20-mg cannabidiol group reported the greatest reduction from baseline in drop-seizure frequency during treatment.
The primary outcome included the percentage change from baseline in the frequency of drop seizures, an average per 28 days, during treatment period.
“Our data from this study provides important insights about the dosage the can provide the best balance between effective seizure control and minimal side effects,” Devinsky said.
Researchers reported that side effects occurred in 94% of patients in the 20-mg group, 84% in the 10-mg group and 72% of those in prescribed placebo.
The effects described were mild or moderate in severity, and those that occurred in more than 10% of patients included somnolence, decreased appetite, diarrhea, upper respiratory infection, fever, vomiting, nasopharyngitis and status epilepticus.
Among the cannabidiol-prescribed patients, 14 experienced dose-related elevated liver aminotransferase concentrations; 7 participants withdrew from the cannabidiol group due to side effects compared to 1 participant in the placebo group.
Currently, only 6 medications are approved to treat seizures in patients with the syndrome, however, disabling seizures occur in most patients despite treatment.
“This treatment would be available for patients with Dravet and Lennox-Gastaut syndromes, 2 rare but very severe childhood-onset epilepsies,” Devinsky added. “This will be a historical event in US medical history as it will be the first cannabis-based product to become FDA approved.”
In April, a US Food and Drug Administration (FDA) advisory panel unanimously voted to recommend approval of a new drug application for Epidiolex cannabidiol oral solution.
The FDA will come to a conclusion on whether to approve the medication in late June.
The study "Effect of Cannabidiol on Drop Seizures in the Lennox—Gastaut Syndrome" was published in The New England Journal of Medicine.