The results of the phase 3 trial (NCT02224703) for cannabidiol (Epidiplex, GW Pharmaceuticals, Carlsbad, CA) show cannabidiol reduced convulsive seizure frequency in children with seizures associated with Dravet syndrome (DS). Cannabidiol is the first prescription for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or DS in individuals age 2 years or more. Cannabidiol is plant-derived cannabis based medicine approved by the Food and Drug Administration (FDA)
In the study, 2 doses of cannabidiol, 10 and 20 mg/kg/day, significantly reduced convulsive seizure frequency compared with placebo in children ages 2 to 18 years with highly treatment-resistant DS, meeting the study’s primary endpoint. The primary endpoint outcomes for the 10 and 20 mg/kg/day arms were similar, with seizure reductions of 49% and 46% from baseline, respectively, vs 27% for placebo (10 mg/kg/day, P=.0095 and 20 mg/kg/day, P=.0299).
“Dravet syndrome is one of the most difficult-to-treat forms of epilepsy and patients are highly individualized in their symptoms and dosing needs,” said Ian Miller, MD, chief of Neurology at Nicklaus Children's Hospital in Miami, FL and lead author. “The data published by JAMA Neurology show that cannabidiol 10 and 20 mg/kg/day were both efficacious and significantly reduced convulsive seizures. Drug resistant seizures are common with DS and it is valuable to have a range of approved doses that offer physicians the flexibility to adjust treatment to a patient’s specific needs.”
Results from key secondary endpoints also showed:
• Significant reductions in total seizure frequency from baseline: 56% for 10 mg/kg/day and 47% for 20 mg/kg/day vs 30% for placebo (P=.0003 and P=.0255, respectively).
• Significantly more individuals taking cannabidiol (44% on 10 mg/kg/day and 49% on 20 mg/kg/day) achieved a 50% or greater reduction in convulsive seizures from baseline during the treatment period compared with placebo (26%; P=.0332 and P=.0069, respectively).
• Compared with placebo, caregivers of individuals treated with cannabidiol were significantly more likely to report an improvement in overall condition as measured by the caregiver global impression of change (CGIC) scale at last visit (10 mg/kg/day, P=.0009 and 20 mg/kg/day, P=.0279).
The most common adverse reactions in the study, occurring in at least 10% of patients in any group, included decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. Elevated liver transaminases occurred more frequently on 20 mg/kg/day than 10 mg/kg/day cannabidiol, with all affected patients on concomitant valproate.
“Epidiolex continues to represent an important advancement in the treatment of difficult-to-treat pediatric onset epilepsies such as DS where there are few FDA approved therapies,” said Justin Gover, GW chief executive officer. “We are pleased that the full results of our GWPCARE2 study in DC are now available to the greater neurology community. The continued publication of our data is a testament to our groundbreaking research in the field of cannabinoids, which we plan to continue to advance in an effort to bring more novel treatments to patients in need.”
Alexis Dallara-Marsh, MD
Natalia P. Rocha, PharmD, MSc, PhD; Gabriela D. Colpo, PhD; Antonio L. Teixeira, MD, PhD, MSc; and Erin Furr Stimming, MD
Stephen M. Gollomp, MD, and Paul G. Mathew, MD, DNBPAS, FAAN, FAHS