London, UK; 17 June 2014: GW Pharmaceuticals a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, today announced physician reports of efficacy and safety data on 27 children and young adults with treatment-resistant epilepsy who have been treated with GW’s investigational cannabidiol (CBD) product candidate, Epidiolex®, for a period of 12 weeks. The treatment-resistant patients suffer from a range of epilepsies in which current anti-epileptic drugs have been unsuccessful in adequately controlling seizures, and included such severe forms of epilepsy as Dravet syndrome and Lennox-Gastaut syndrome. Uncontrolled data from two hospital sites in the United States that were generated under expanded access Investigational New Drug applications (INDs) authorized by the Food and Drug Administration (FDA) were made available to the Company.
“We are pleased to report preliminary data on Epidiolex which provides promising signals of efficacy in children with treatment-resistant epilepsy, including patients with Dravet syndrome. It is noteworthy that, of the patients who have responded to Epidiolex, a high proportion show a reduction in seizure frequency of greater than 50% and a portion of these patients were reported to be seizure-free at the end of 12 weeks of treatment,” stated Justin Gover, GW’s Chief Executive Officer. “We believe that these signals of efficacy, together with the side effect profile observed to date, support GW’s decision to advance Epidiolex into a formal development program and we look forward to commencing a Phase 2/3 clinical trial of Epidiolex in Dravet syndrome in the second half of 2014.”
“There remains an enormous unmet need in a range of pediatric and adult treatment-resistant epilepsy syndromes, which affect approximately 750,000 Americans. Some of the greatest needs are in children with severe epilepsy syndromes such as Dravet and Lennox-Gastaut, where frequent seizures often persist despite high doses of multiple anti-epileptic drugs,” stated Orrin Devinsky MD, Professor of Neurology, Neurosurgery, and Psychiatry at NYU School of Medicine, and Director, NYU Comprehensive Epilepsy Center. “The initial open-label study with Epidiolex has provided encouraging results. Some children have had marked reductions in their seizures and overall, the medication has been well tolerated.”
Data were made available on 27 patients whom have been treated with Epidiolex for at least 12 weeks. Two patients commenced treatment in 2013 and the remaining 25 patients commenced treatment in the first quarter of 2014. All patients were treated at New York University Langone Medical Center (NYU) or the University of California at San Francisco (UCSF). Treatment effect data have been calculated in a manner consistent with the FDA’s recommended endpoint for evaluating efficacy, which compares percent change in the average 4 week seizure frequency throughout the 12 week treatment period to seizure frequency during a 4 week baseline period. The same approach of average 4 week seizure frequency throughout the 12 week treatment period has been used in a responder analysis.
In addition, safety data have been collected to date on a total of 62 patients (27 patients with 12 weeks treatment plus 35 additional patients who have commenced treatment under the expanded access treatment program but have yet to reach 12 weeks of treatment from NYU, UCSF and Massachusetts General Hospital in Boston).
Data were collected at hospital sites by the local medical teams and sent to GW for compiling into a database. It should be noted that expanded access studies, sometimes called “compassionate use”, are uncontrolled, carried out by individual investigators, not conducted in strict compliance with Good Clinical Practices and not intended to be analyzed together as study data. Therefore, the data reported from these programs may not be indicative of results from, or duplicated in, placebo-controlled company-sponsored clinical trials.
Epilepsy Types and Demographics
Of the 27 patients, the largest single type of epilepsy was Dravet syndrome (n=9). The remaining patients comprise a range of treatment-resistant epilepsies with convulsive and/or non-convulsive seizures.
The 27 patients were predominately children with an average age of 10.5 years (26 of the 27 patients were between 3 to 18 years of age, and 1 patient was 26 years of age). In all cases, Epidiolex was added to current anti-epileptic drugs (AEDs). On average, patients were taking 2.7 other AEDs.
Clinical Effect Data – All Patients
Data were made available on all 27 patients and includes information collected on all seizures (convulsive and non-convulsive) reported for each patient.
- The mean overall reduction in seizure frequency as compared to baseline seizure frequency was 44% and median overall reduction in seizure frequency as compared to baseline seizure frequency was 42%
- 48% of all patients obtained at least a 50% reduction in seizure frequency as compared to baseline seizure frequency
- 41% of all patients obtained at least a 70% reduction in seizure frequency as compared to baseline seizure frequency
- 22% of all patients obtained at least a 90% reduction in seizure frequency as compared to baseline seizure frequency
- At the end of 12 weeks, 15% of all patients were seizure-free
Clinical Effect Data – Dravet syndrome patients only
With respect to the 9 patients with Dravet syndrome, the data presented below include only convulsive seizures reported for each patient, the only types of seizures considered by FDA in assessing primary efficacy for Dravet syndrome trials. The 9 patients with Dravet syndrome ranged from 3 years to 16 years of age with an average of age of 8.3 years.
- The mean reduction in seizure frequency as compared to baseline seizure frequency was 52% and median reduction in seizure frequency as compared to baseline seizure frequency was 63%
- 56% of Dravet patients obtained at least a 50% reduction in seizure frequency as compared to baseline seizure frequency
- 44% of Dravet patients obtained at least a 70% reduction in seizure frequency as compared to baseline seizure frequency
- 33% of Dravet patients obtained at least a 90% reduction in seizure frequency as compared to baseline seizure frequency
- At the end of 12 weeks, 33% of Dravet patients were seizure-free
Safety data were made available on 62 patients and represents approximately 120 patient-months of treatment with Epidiolex.
- At least one adverse event was reported in 81% (50) of patients
- The most common adverse events (occurring in 10% or more patients and resulting from all causes) were:
- Somnolence 40% of patients
- Fatigue 26% of patients
- Diarrhea 16% of patients
- Decreased appetite 11% of patients
- Increased appetite 10% of patients
- 80% of reported adverse events were mild or moderate
- There were no withdrawals from treatment due to adverse events
- There was 1 withdrawal from treatment due to lack of clinical effect. An additional 2 patients are currently being gradually withdrawn from treatment after 3 months due to lack of clinical effect
- Serious adverse events were reported in 7 patients, including 1 death of a patient from SUDEP (sudden unexpected death in epilepsy). None of these serious adverse events, including the 1 reported death, were deemed related to Epidiolex by the independent investigators
- In some instances, the addition of Epidiolex may be associated with changes in serum concentrations of concomitant anti-epileptic drugs
In addition to the expanded access IND patients, 5 patients have commenced treatment with Epidiolex under emergency access INDs. GW has received information from the treating physicians that 3 of these patients reported perceived benefits after treatment with Epidiolex and all 5 patients remain on treatment.
GW Development Program
GW is developing Epidiolex in the treatment of Dravet syndrome, for which the Company has received both orphan drug designation and Fast Track designation from the FDA. A company-sponsored IND is open with the FDA and a Phase 2/3 trial is expected to commence in the second half of 2014. GW anticipates commencing an additional Phase 3 trial in Dravet syndrome in the first quarter of 2015. 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, GW expects to hold a pre-IND meeting with the FDA for Epidiolex in the treatment of LGS in mid-2014, and expects to conduct two Phase 3 trials in LGS during 2015.