The positive results of the first pivotal phase 3 study of the investigational medicine Epidiolex ( Cannabidiol or CBD ) for the treatment of Dravet syndrome were announced.
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 antiepileptic drugs, having previously tried and failed an average of more than 4 other antiepileptic drugs.
The average age of trial participants was 10 years and 30% of patients were less than 6 years of age.
The median baseline convulsive seizure frequency per month was 13.
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% compared with a reduction on placebo of 13%, 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.
Results from secondary efficacy endpoints reinforced the overall effectiveness observed with Epidiolex.
Epidiolex was generally well tolerated in this study. The most common adverse events ( occurring in greater than 10% 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% 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.
Dravet syndrome is a severe infantile-onset and highly treatment-resistant epileptic syndrome frequently associated with a genetic mutation in sodium channels. Onset of Dravet syndrome occurs during the first year of life in previously healthy and developmentally normal infants. Initial seizures are often temperature related, severe, and long-lasting. Over time, people with Dravet syndrome can develop multiple types of seizures, including tonic-clonic, myoclonic, and atypical absences and are prone to bouts of prolonged seizures called status epilepticus, which can be life threatening.
Risk of premature death including SUDEP ( sudden expected death in epilepsy ) is elevated in people with Dravet Syndrome.
Additionally, the majority will develop moderate to severe intellectual and development disabilities and require lifelong supervision and care.
There are currently no FDA-approved treatments and nearly all patients continue to have uncontrolled seizures and other medical needs throughout their lifetime.
Epidiolex, cannabinoid product candidate, is a liquid formulation of pure plant-derived CBD, which is in development for the treatment of a number of rare pediatric epilepsy disorders.
CBD has significant anti-epileptiform and anticonvulsant activity using a variety of in vitro and in vivo models and has the ability to treat seizures in acute animal models of epilepsy with significantly fewer side effects than existing anti-epileptic drugs. ( Xagena )
Source: GW Pharmaceuticals, 2016