Positive results have been reported from a phase 3, randomized, double-blind, placebo-controlled study of the investigational medication Epidiolex (cannabidiol, GW Pharmaceuticals) in the treatment of patients with Lennox–Gastaut syndrome (LGS), a rare and severe form of childhood-onset epilepsy. In this study, Epidiolex, when added as an adjunct to the patient’s current treatment, achieved the primary endpoint of a significant reduction in the monthly frequency of drop seizures assessed over the 14-week treatment period compared with placebo (P = 0.0135). Epidiolex has an orphan drug designation from the FDA for the treatment of LGS.
Patients two to 55 years of age with a confirmed diagnosis of drug-resistant LGS currently uncontrolled on one or more concomitant anti-epileptic drugs (AEDs) were eligible to participate in the study. A total of 171 patients were randomly assigned to two treatment arms in which Epidiolex 20 mg/kg/day (n = 86) or placebo (n = 85) was added to current AED treatment. On average, the patients were taking approximately three AEDs, having previously tried and failed an average of six other AEDs. The patients’ average age was 15 years, and 34% were 18 years of age or older. The median baseline drop seizure frequency per month was 74.
The study’s primary efficacy endpoint was the percentage change in the monthly frequency of drop seizures during the 14-week treatment period (a two-week dose escalation period followed by 12 weeks of maintenance therapy) compared with the four-week baseline period before randomization. Drop seizures were defined as atonic, tonic, and tonic-clonic seizures involving the entire body, trunk, or head that led or could have led to a fall, injury, slumping in a chair, or hitting the patient’s head on a surface. During the treatment period, patients treated with Epidiolex achieved a median reduction in monthly drop seizures of 44% compared with a reduction of 22% in patients receiving placebo (P = 0.0135).
Epidiolex was generally well tolerated. Overall, 86% of the Epidiolex-treated patients experienced an adverse event compared with 69% percent of the patients given placebo. The most common adverse events included diarrhea, somnolence, decreased appetite, pyrexia, and vomiting. Of the patients receiving Epidiolex who reported an adverse event, 78% reported the event to be mild or moderate in severity. Twenty patients (23%) treated with Epidiolex experienced a serious adverse event (nine of which were deemed to be treatment-related) compared with four patients (5%) receiving placebo (one of which was deemed to be treatment-related). Twelve patients (14%) treated with Epidiolex discontinued treatment because of adverse events compared with one patient (1%) receiving placebo. There was one death in the Epidiolex group, which was deemed to be unrelated to treatment. Of the patients who completed this trial, 100% have opted to continue into an open-label extension trial.
Source: GW Pharmaceuticals; June 27, 2016.