LONDON—Following on successful Phase 3 trial data in March for Dravet syndrome, investigational medicine Epidiolex (cannabidiol or CBD) from GW Pharmaceuticals plc showed some potential mettle yet again with data reported June 27 from a Phase 3 trial of the therapeutic in treating Lennox-Gastaut syndrome (LGS), a rare and severe form of childhood-onset epilepsy. Epidiolex has Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of both LGS and Dravet syndrome.
GW—a a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform—said that in this first randomized, double-blind, placebo-controlled Phase 3 clinical trial of Epidiolex for the treatment of LGS, the drug, 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.
“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 Dr. Linda Laux, director of the Comprehensive Epilepsy Center at Ann & Robert H. Lurie Children's Hospital of Chicago and assistant professor of pediatrics at the 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 CEO. “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 LGS Foundation. “We are thrilled with these positive results, which offer much needed hope and promise to those living with this debilitating condition."
Patients aged 2 to 55 years with a confirmed diagnosis of drug-resistant LGS currently uncontrolled on one or more concomitant antiepileptic drugs (AEDs) were eligible to participate in this trial. The trial randomized 171 patients into two arms, where Epidiolex 20mg/kg/day or placebo was added to current AED treatment. On average, patients were taking approximately three AEDs, having previously tried and failed an average of six other AEDs. The average age of trial participants was 15 years (34 percent were 18 years or older). The median baseline drop seizure frequency per month was 74.
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.
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.
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.
The peak onset of LGS typically occurs between the ages of 3 and 5 and can be caused by a number of conditions, including brain malformations, severe head injuries, central nervous system infections and inherited degenerative or metabolic conditions. In up to 30 percent of patients, no cause can be found. Patients with LGS commonly have multiple seizure types including non-convulsive, convulsive and drop seizures, which frequently lead to falls and injuries. Drug resistance is one of the main features of LGS. Most children with LGS experience some degree of impaired intellectual functioning, as well as developmental delays and behavioral disturbances. It is estimated that there are approximately 14,000 to 18,500 patients with LGS in the United States and 23,000 to 31,000 patients with LGS in Europe.
Epidiolex is GW’s lead cannabinoid product candidate, an oral pharmaceutical formulation of pure CBD, which is in development for the treatment of a number of rare childhood-onset epilepsy disorders. GW has conducted extensive pre-clinical research of CBD in epilepsy since 2007. This research has shown that CBD has significant anti-epileptiform and anticonvulsant activity using a variety of in-vitro and in-vivo models and reduced seizures in various acute animal models of epilepsy.
In addition to the Orphan Drug Designation from the FDA for Epidiolex for Dravet syndrome and LGS, it also gained that status for tuberous sclerosis complex and infantile spasms. Additionally, GW has received Fast Track Designation from the FDA and Orphan Designation from the European Medicines Agency for Epidiolex for the treatment of Dravet syndrome. GW is currently evaluating additional clinical development programs in other orphan seizure disorders.
Leerink Partners analysts were upbeat about the prospects for the drug and for GW after trial results were announced, and remained positive following a conference call. The firm raised its price target for the publicly traded company to $138 from $130 on a higher probability-of-success in LGS (now up to 85 percent from 75 previously) and a slightly higher probability of approval in Dravet (up to 90 precent from 85 perecent, and Leerink reiterated its Outperform rating for GW.