GW Pharmaceuticals announces positive Phase 3 pivotal trial results for Epidiolex® (cannabidiol) in the treatment of Lennox-Gastaut syndrome.
GW Pharmaceuticals plc, a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, announces positive results of the first randomized, double-blind, placebo-controlled Phase 3 clinical trial of its investigational medicine Epidiolex® (cannabidiol or CBD) for the treatment of Lennox-Gastaut syndrome (LGS), a rare and severe form of childhood-onset epilepsy.
In this trial, 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 entire 14-week treatment period compared with placebo (p=0.0135). This trial follows the announcement in March 2016 of positive results in a pivotal Phase 3 trial of Epidiolex for the treatment of Dravet syndrome. Epidiolex has Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of LGS and Dravet syndrome.
“From a physician’s perspective, the positive outcome in this trial of Epidiolex in patients with Lennox-Gastaut syndrome is very exciting. Lennox-Gastaut syndrome begins in early childhood, is particularly difficult to treat, and the vast majority of patients do not obtain an adequate response from existing therapies,” stated Linda Laux, MD, Director of the Comprehensive Epilepsy Center at Ann & Robert H. Lurie Children’s Hospital of Chicago and assistant professor of pediatrics, Northwestern University Feinberg School of Medicine and an investigator in the trial. “These data show that Epidiolex has the potential to provide a robust and clinically meaningful reduction in seizures in this highly treatment-resistant population together with an acceptable safety and tolerability profile, which is consistent with my previous clinical experience with Epidiolex. I am excited about the prospect of Epidiolex being made available on prescription in the future and believe it has the potential to make an important difference to the lives of many patients.”
“We are delighted to announce positive results in this Phase 3 trial of Epidiolex in patients with Lennox-Gastaut syndrome, and particularly pleased that this result is consistent with our recent Phase 3 pivotal data for Epidiolex in Dravet syndrome. We believe that this result further demonstrates that Epidiolex offers the potential to be a new effective therapy within the field of treatment-resistant childhood-onset epilepsies,” stated Justin Gover, GW’s Chief Executive Officer. “We now look forward to advancing Epidiolex towards the submission of an NDA with the FDA in the first half of 2017.”
“Lennox-Gastaut syndrome is such a difficult form of epilepsy to treat. Additional safe and effective treatments are desperately needed for patients who continue to struggle with uncontrolled seizures,” said Christina SanInocencio, Executive Director of the Lennox-Gastaut Syndrome Foundation. “We are thrilled with these positive results, which offer much needed hope and promise to those living with this debilitating condition.”
Trial Overview and Result
Patients aged 2-55 years with a confirmed diagnosis of drug-resistant LGS currently uncontrolled on one or more concomitant anti-epileptic drugs (AEDs) were eligible to participate in this Phase 3, randomized, double-blind placebo-controlled trial. The trial randomized 171 patients into two arms, where Epidiolex 20mg/kg/day (n=86) or placebo (n=85) was added to current AED treatment. On average, patients were taking approximately 3 AEDs, having previously tried and failed an average of 6 other AEDs. The average age of trial participants was 15 years (34% were 18 years or older). The median baseline drop seizure frequency per month was 74.
The primary efficacy endpoint of this trial was a comparison between Epidiolex and placebo in the percentage change in the monthly frequency of drop seizures during the 14 week treatment period (2 week dose escalation period followed by 12 weeks of maintenance) compared to the 4 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 taking Epidiolex achieved a median reduction in monthly drop seizures of 44 percent compared with a reduction of 22 percent in patients receiving placebo, and the difference between treatments was statistically significant (p=0.0135).
A series of sensitivity analyses of the primary endpoint confirmed the robustness of this result. The difference between Epidiolex and placebo emerged during the first month of treatment and was sustained during the entire treatment period. Results from secondary efficacy endpoints reinforced the overall effectiveness observed with Epidiolex.
Epidiolex was generally well tolerated in this trial. Overall, 86 percent of all Epidiolex patients experienced an adverse event compared with 69 percent of patients on placebo. The most common adverse events (occurring in greater than 10 percent of Epidiolex-treated patients) were: diarrhea, somnolence, decreased appetite, pyrexia, and vomiting. Of those patients on Epidiolex who reported an adverse event, 78 percent reported it to be mild or moderate. Twenty patients on Epidiolex experienced a serious adverse event (nine of which were deemed treatment related) compared with four patients on placebo (one of which was deemed treatment related). Twelve patients on Epidiolex discontinued treatment due to adverse events compared with one patient on placebo. There was one death in the Epidiolex group, which was deemed unrelated to treatment. Of the patients who completed this trial, 100 percent have opted to continue into an open-label extension trial.
Further data will be presented in future publications and medical meetings.
In addition to this first Phase 3 trial of Epidiolex in LGS, GW is conducting a second Phase 3 dose-ranging trial of Epidiolex for the treatment of LGS, which is fully enrolled at 225 patients. This second trial has three treatment arms: Epidiolex 20mg/kg/day, 10mg/kg/day and placebo. GW expects to report top-line results from this trial towards the end of the third quarter of this year.
Filed Under: Drug Discovery