Positive results have been reported from a phase 3 study of the investigational medication cannabidiol (Epidiolex, GW Pharmaceuticals) in patients with Dravet syndrome, a rare and debilitating type of infantile-onset epilepsy for which no treatments are currently available in the U.S. Cannabidiol achieved the trial’s primary endpoint of a significant reduction in convulsive seizures assessed over the entire treatment period compared with placebo (P = 0.01). Cannabidiol has received both orphan-drug and fast-track designations for the treatment of Dravet syndrome.
Epidiolex is a liquid formulation of plant-derived cannabidiol, which is in development for the treatment of rare pediatric epilepsy disorders.
The pivotal study randomly assigned 120 patients to two treatment arms: cannabidiol 20 mg/kg per day (n = 61) or placebo (n = 59). Cannabidiol or placebo was added to current antiepileptic drug (AED) treatment regimens. On average, the patients were taking approximately three AEDs, having previously tried and failed an average of more than four other AEDs. The trial participants’ average age was 10 years, and 30% of the participants were less than 6 years of age. The median baseline convulsive seizure frequency per month was 13.
The study’s primary efficacy endpoint was the percent change in the monthly frequency of convulsive seizures during the 14-week treatment period compared with the four-week baseline observation period in the cannabidiol and placebo groups. Patients treated with cannabidiol achieved a median reduction in monthly convulsive seizures of 39% compared with a reduction of 13% among those given placebo (P = 0.01). The difference between cannabidiol and placebo emerged during the first month of treatment and was sustained during the 14-week treatment period.
The most common adverse events (AEs) associated with cannabidiol included somnolence, diarrhea, decreased appetite, fatigue, pyrexia, vomiting, lethargy, upper respiratory tract infection, and convulsions. Of the cannabidiol-treated patients who reported an AE, 84% described the event as mild or moderate in severity. Ten patients treated with cannabidiol experienced a serious AE compared with three patients given placebo. Eight patients in the cannabidiol arm discontinued treatment because of AEs compared with one patient in the placebo arm.
Dravet syndrome is a severe infantile-onset and highly treatment-resistant epileptic syndrome often associated with a genetic mutation in sodium channels. The onset of Dravet syndrome occurs during the first year of life in previously healthy and developmentally normal infants. Initial seizures are often temperature-related, severe, and long-lasting. Over time, patients with Dravet syndrome can develop multiple types of seizures, including tonic-clonic, myoclonic, and atypical absences, and are prone to bouts of prolonged seizures (status epilepticus), which can be life threatening.
The risk of premature death, including sudden expected death in epilepsy (SUDEP), is elevated in patients with Dravet syndrome. In addition, most patients will develop moderate-to-severe intellectual and development disabilities and will require lifelong supervision and care. No FDA-approved treatments are currently available for patients with Dravet syndrome, and nearly all patients continue to have uncontrolled seizures and other medical needs throughout their lifetimes.
Source: GW Pharmaceuticals; March 14, 2016.