Date: 2016-03-14
Type of information: Results
phase: 3
Announcement: results
Company: GW Pharmaceuticals (UK)
Product: Epidiolex® (cannabidiol (2-[(1R,6R)-3-Methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol)
Action
mechanism: cannabinol derivative/endocannabinoid modulator. Epidiolex® has both Orphan Drug Designation and Fast Track Designation from the FDA in the treatment of Dravet syndrome. The EMA has also granted orphan drug designation for Epidiolex® for use in the treatment of this disease.
Disease: Dravet syndrome
Therapeutic area: Rare diseases
Country: USA
Trial
details: The Phase 2/3 trial is a two-part randomized double-blind, placebo-controlled parallel group dose escalation, safety, tolerability, pharmacokinetic and efficacy trial of single and multiple doses of Epidiolex® to treat Dravet syndrome in children who are being treated with other anti-epileptic drugs. Part one comprises the pharmacokinetic and dose-finding elements of the trial in a total of 30 patients over a 3 week treatment period. Part two is a placebo-controlled safety and efficacy evaluation of Epidiolex® over a 3 month treatment period in a total of 80 patients. All patients who participate in the study will be eligible to receive Epidiolex® under a long term open label extension protocol.
Latest
news: * On March 14, 2016, GW Pharmaceuticals announced results of the first pivotal Phase 3 study of Epidiolex® (cannabidiol or CBD) for the treatment of Dravet syndrome. In this study, Epidiolex® achieved the primary endpoint of a significant reduction in convulsive seizures assessed over the entire treatment period compared with placebo (p=0.01). The Phase 3 study randomized 120 patients into two arms, Epidiolex® 20mg/kg/day (n=61) and placebo (n=59). Epidiolex® or placebo was added to current anti-epileptic drug (AED) treatment regimens. On average, patients were taking approximately 3 AEDs, having previously tried and failed an average of more than 4 other AEDs. The average age of trial participants was 10 years and 30 percent of patients were less than 6 years of age. The median baseline convulsive seizure frequency per month was 13. * On April 21, 2015, GW Pharmaceuticals announced that it has initiated the second Phase 3 clinical trial of Epidiolex® (cannabidiol or CBD) for the treatment of Dravet syndrome, a rare and catastrophic treatment-resistant form of childhood epilepsy. This follows GW’s recent announcement of the commencement of the first Phase 3 clinical trial of Epidiolex in Dravet syndrome. GW expects to complete patient recruitment into this second trial in 2015 and to report top-line results in early 2016. * On March 31, 2015, GW Pharmaceuticals announced it has initiated the Phase 3 part of a Phase 2/3 clinical trial of Epidiolex® (cannabidiol or CBD) for the treatment of Dravet syndrome. GW anticipates that top-line data from this trial will be available around the end of 2015. The Phase 3 trial is the second part of a two-part randomized double-blind, placebo-controlled parallel group safety, tolerability, pharmacokinetic and efficacy trial of Epidiolex to treat Dravet syndrome in children who are being treated with other anti-epileptic drugs. Part one completed in February 2015 and comprised the pharmacokinetic and dose-finding elements of the trial in a total of 34 patients over a three week treatment period. The dose for part two has been determined as 20mg/kg by a Data Safety Monitoring Committee (DSMC) after assessment of the part one safety and pharmacokinetic data. * On October 30, 2014, GW Pharmaceuticals announced it has commenced a Phase 2/3 clinical trial of Epidiolex® (cannabidiol or CBD) for the treatment of Dravet syndrome. GW anticipates commencing an additional Phase 3 trial in Dravet syndrome in the first quarter of 2015 in parallel with part two of the first Phase 2/3 trial. The company also expects to commence two Phase 3 clinical trials in Lennox-Gastaut syndrome in the first quarter of 2015. * On May 7, 2014, GW Pharmaceuticals announced that the Company has received confirmation from the FDA that its Investigational New Drug application (IND) is now open for Epidiolex® in the treatment of Dravet Syndrome, a rare treatment-resistant form of childhood epilepsy. GW expects to commence a Phase 2/3 clinical trial in the second half of 2014. GW anticipates commencing an additional Phase 3 trial in Dravet syndrome in the first quarter of 2015 in parallel with part two of the first Phase 2/3 trial. In addition to Dravet syndrome, GW plans to conduct a clinical development program for Epidiolex® in the treatment of Lennox-Gastaut syndrome (LGS). Following receipt earlier in 2014 of orphan drug designation by the FDA in LGS, GW expects to hold a pre-IND meeting with the FDA for Epidiolex® in the treatment of LGS in mid-2014, and aims to conduct two Phase 3 trials in LGS during 2015. Epidiolex® has already received orphan drug designation from the FDA for the treatment of Dravet syndrome.
The primary efficacy endpoint was a comparison between Epidiolex® and placebo measuring the percentage change in the monthly frequency of convulsive seizures during the 14-week treatment period compared with the 4-week baseline observation period. In this study, patients taking Epidiolex® achieved a median reduction in monthly convulsive seizures of 39 percent compared with a reduction on placebo of 13 percent, which was highly statistically significant (p=0.01). 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.
Epidiolex® was generally well tolerated in this study. The most common adverse events (occurring in greater than 10 percent of Epidiolex-treated patients) were: somnolence, diarrhea, decreased appetite, fatigue, pyrexia, vomiting, lethargy, upper respiratory tract infection and convulsion. Of those patients on Epidiolex® that reported an adverse event, 84 percent reported it to be mild or moderate. Ten patients on Epidiolex® experienced a serious adverse event compared with three patients on placebo. Eight patients on Epidiolex® discontinued treatment due to adverse events compared with one patient on placebo. Further data will be presented in future publications and medical meetings.
GW Pharmaceuticals will now request a pre-NDA meeting with the FDA to discuss our proposed regulatory submission. In addition to this first Phase 3 trial, GW is conducting a second Phase 3 trial in Dravet syndrome which is recruiting 150 patients.
The Phase 3 trial is a 14-week comparison of Epidiolex versus placebo in a total of 150 patients to assess the safety and efficacy as an adjunctive antiepileptic treatment. This Phase 3 trial will have three treatment arms of equal patient numbers; 20mg/kg of Epidiolex, 10mg/kg of Epidiolex, and placebo. The primary measure of this trial will be the percentage change from baseline in convulsive seizure frequency during the maintenance period of the study in patients taking Epidiolex versus placebo. Several additional efficacy and safety secondary outcome measures will be analysed. Following their participation in the study, all patients are eligible to receive Epidiolex under a long term open label extension study.
Part two is a 14-week comparison of Epidiolex versus placebo in a total of 100 patients to assess the safety and efficacy as an adjunctive antiepileptic treatment. The primary measure of this trial will be the percentage change from baseline in convulsive seizure frequency during the maintenance period of the study in patients taking Epidiolex versus placebo. Several additional efficacy and safety secondary outcome measures will be analysed. Part two will recruit an entirely new group of patients who did not participate in part one. Following their participation in the study, all patients are eligible to receive Epidiolex under a long term open label extension study.
GW anticipates commencing the second pivotal Phase 3 trial in Dravet syndrome soon after this first trial, which will run in parallel with this Phase 2/3 trial. The Company also expects to commence two Phase 3 clinical trials in Lennox-Gastaut syndrome early in the second quarter of 2015. These additional pivotal trials are all expected to complete recruitment in 2015.
