Advisory committee member Dr. Mendelson asked for long-term monitoring, noting that “we need to watch for long-term safety data because this is a novel drug.”
The FDA’s re-analysis of data from 3 randomized, double-blind, placebo-controlled trials agreed with the efficacy findings reported by GW Pharmaceuticals. Cannabidiol oral solution met its primary endpoint of a reduction in frequency of seizures in LGS and DS patients in all 3 pivotal clinical trials, showing a significant improvement in seizure control when added to standard of care antiepileptic drug therapy for patients with drug-resistant LGS and DS.
The safety evaluation was based on a total of 1,756 patients who were exposed to cannabidiol oral solution, “adequate exposure to allow for assessment of safety,” said Natalie Getzoff, MD, a clinical review in the CDER’s Division of Neurology Products. Though 20 deaths were seen in the study population, “overall, the causes of death were varied and not unexpected for the patient population, and not clearly linked to the drug,” she said. “At this point in our review, we have not identified any obstacles to approval.”
To be included in the clinical trials, LGS patients had to be 2-55 years old, using at least one antiepileptic drug and still having at least 8 drop seizures every 4 weeks and at least two drop seizures weekly. DS patients were aged 2-18 years old, also using at least one antiepileptic drug at baseline and having at least 4 convulsive seizures in a 4 week period.
A total of 235 patients with LGS and 88 patients with DS were enrolled in the clinical trials, and an additional 157 patients with LGS and 209 patients with DS were enrolled in the open-label extension study.
An expanded access program for individuals with refractory epilepsy is ongoing, and 684 patients have been enrolled to date, including 97 LGS patients and 64 DS patients.
The proposed indications for cannabidiol oral solution are for the adjunctive treatment of seizures associated with LGS and DS in patients 2 years of age and older. Initial dosing recommendations are to titrate to a dose of 10 mg/kg/day, with dose adjustments permissible up to 20 mg/kg/day depending on clinical response and tolerability. Cannabidiol received fast track designation in 2014, and rare pediatric designation for LGS and DS in 2017.
The FDA is not obligated to support the recommendations of its advisory committees, though it often does. The agency is slated to take action on cannabidiol oral solution by June.
This article was updated 4/19/18.