Rare Daily Staff
The New England Journal of Medicine has published results from a late-stage study of GW Pharmaceuticals Epidiolex in patients with Lennox-Gastaut syndrome, a rare, severe and difficult to treat form of childhood-onset epilepsy.
LGS is a lifelong form of epilepsy that begins in childhood and is associated with a high mortality rate, and significant developmental delays. LGS patients suffer from multiple types of seizures, including drop seizures which can result in falls and other injuries. Results from this study represent the only well-controlled clinical evaluation of a pharmaceutical cannabinoid medication for this severe, drug-resistant condition.
Epidiolex is a pharmaceutical formulation of highly purified cannabidiol, a cannabinoid lacking the high associated with marijuana. Epidiolex is also being studied for the treatment of a number of other rare, severe childhood-onset epilepsy disorders.
A U.S. Food and Drug advisory committee on April 19 unanimously recommended approval of Epidiolex to treat patients with LGS and another rare childhood-onset epilepsy known as Dravet syndrome. The U.S. Food and Drug Administration is expected by the end of June to rule on GW’s application for marketing approval.
“This publication in the New England Journal of Medicine marks the third time within a year that positive data for Epidiolex have been published by a top-tier, peer-reviewed journal, offering further evidence of the potential of Epidiolex as a new treatment option within the field of treatment-resistant, childhood-onset epilepsy,” said Justin Gover, GW’s CEO.
The study randomized 225 patients with LGS whose seizures were not controlled by their current anti-epileptic drug regimen, to receive either one of two doses of Epidiolex or placebo in addition to existing treatment. The average age of trial participants was 16 years (30 percent were 18 years or older). The study was conducted in 30 centers in the United States and Europe, and on average, patients were taking three concomitant anti-epileptic drug regimens.
Both doses significantly reduced the monthly frequency of drop seizures compared to placebo in highly treatment-resistant patients when added to existing treatment. At baseline, patients had a median frequency of 85 drop seizures per month.
The primary efficacy endpoint of this trial was the percentage change from baseline in monthly drop seizure frequency during the treatment period. Sensitivity analyses confirmed that the treatment effect of Epidiolex was established during the first month of treatment and was sustained over the entire treatment period.
Results from key secondary endpoints showed that a significant number of patients receiving Epidiolex at the lower of two doses (36 percent) and at the higher of two doses (39 percent) experienced a 50 percent or greater reduction in monthly drop seizures compared with those taking placebo. In addition, patients/caregivers were significantly more likely to report an improvement in overall condition with both Epidiolex doses compared to placebo.
The proportion of patients who experienced at least a 75 percent reduction from baseline in drop seizure frequency was greater in the higher dose group than the lower dose group (25 percent vs 11 percent). Both were higher when compared with those taking placebo (3 percent).
Epidiolex was generally well tolerated in the trial. The pattern of adverse events was consistent with that reported in previous phase 3 studies. For both dose groups, the adverse events experienced by greater than 10 percent of patients included somnolence, decreased appetite, diarrhea, upper respiratory infection, pyrexia, vomiting, nasopharyngitis, and status epilepticus. None of the cases of status epilepticus in the lower dose group was deemed treatment related.
“These positive data are important in that they provide further evidence of the promise of this investigational treatment in LGS, as well as information on its dosing range that can assist clinicians with prescribing decisions to address individual patient needs should this medicine be approved for use,” said Orrin Devinsky of NYU Langone Health’s Comprehensive Epilepsy Center and lead author of the study. “The growing body of data which support the potential of this cannabidiol treatment in LGS and Dravet syndrome indicates that this treatment may offer meaningful benefit to these patients, who often do not have an adequate response to existing therapies.”
May 17, 2018
Photo: Justin Gover, CEO of GW Pharmaceuticals