Efficacy and safety of Epidiolex, a Cannabidiol product, in children and young adults with treatment-resistant epilepsy
Preliminary efficacy and safety data on 27 children and young adults with treatment-resistant epilepsy who have been treated with an investigational Cannabidiol ( CBD ) product candidate, Epidiolex, for a period of 12 weeks, were presented.
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.
Epidiolex has provided 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 has shown 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.
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 ).
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. On average, patients were taking 2.7 other antiepileptic drugs.
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.
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 represent approximately 120 patient-months of treatment with Epidiolex.
At least one adverse event was reported in 81% ( n=50 ) of patients. The most common adverse events ( occurring in 10% or more patients and resulting from all causes ) were: somnolence ( 40% ); fatigue ( 26% ), diarrhea ( 16% ); decreased appetite ( 11% ); increased appetite ( 10% ).
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. 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. ( Xagena )
Source: GW Pharmaceuticals, 2014
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