CBD Reduces Frequency Of Seizures In Dravet Syndrome

Adding cannabidiol–a cannabinoid with no hallucinogenic properties–to standard drug therapy for young patients with a rare seizure disorder known as Dravet syndrome significantly reduced the frequency of seizures, based on the results of a new industry-funded study.

The findings were published online yesterday in the New England Journal of Medicine.

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With such promising results for Epidiolex, the cannabis-derived drug manufactured by GW Pharmaceuticals for this NEJM study, the company now seems poised to file for FDA approval in the U.S.

Early and encouraging results from a phase 3 trial of the drug to treat Dravet syndrome were published in 2016, adding to enthusiasm about the promise of the drug.

In the paper published today, nearly 43% of children receiving Epidiolex experienced a 50% reduction or greater in frequency of seizures, compared to just 17% of those in the placebo group. And 5% of those taking the drug became seizure-free, compared to none in the placebo group.

This translates to the median number of seizures going from 12 per month to just under 6 compared with placebo, correlating with improvement in quality-of-life scores measured during the study.

“Cannabidiol should not be viewed as a panacea for epilepsy, but for patients with especially severe forms who have not responded to numerous medications, providing hope that we may soon have another treatment option,” said lead investigator Orrin Devinsky, M.D., professor of neurology, neurosurgery and psychiatry, and director of the Comprehensive Epilepsy Center at NYU Langone Medical Center, in a press release. “We still  need more research, but this new trial provides more evidence than we have ever had of cannabidiol’s effectiveness as medication for treatment-resistant epilepsy.”

In an accompanying editorial, Samuel Berkovic, M.D., of the Epilepsy Research Centre at the University of Melbourne in Australia, expressed his enthusiasm for the research, embracing this as the first “real data” demonstrating the clinical utility supporting the use of cannabinoids in the treatment of epilepsy. “Future trials may answer further questions about the applicability of cannabinoids to the many other syndromes of childhood epilepsy and to treatment in adults,” he added.

There are presently no FDA-approved drugs to treat Dravet syndrome, a rare disorder resulting in drug-resistant seizures which can increase risk for death and pulmonary complications, including aspiration pneumonia and resulting sepsis.

5,500 patients are estimated to be affected by Dravet syndrome, with up to 7,000 more patients in Europe. The syndrome typically develops after birth and generally before a child’s first birthday. Mortality is high with the syndrome, with nearly 15% of patients dying before the age of 7, and the bulk of patients with major cognitive impairment and learning disabilities.

In the study, researchers randomized 120 patients 2–18 years of age previously diagnosed with Dravet syndrome to receive the study drug, an oral cannabidiol solution, or placebo, along with their standard antiepileptic medications over a 14-week period.

Results of the study were impressive. Among the children and teens who were treated with cannabidiol along with their standard medications, the median number of monthly convulsive-type seizures decreased from 12.4 at baseline to 5.9 over the 14-week period. Meanwhile, study participants in the placebo group had minimal change in their monthly frequency, from 14.9 to 14.1. However, cannabidiol did not reduce the frequency of nonconvulsive seizures between the two study groups.

One downside to treatment with cannabidiol was the increase in adverse events, which were observed with greater frequency in those receiving cannabidiol compared to placebo (93% vs. 75%). Examples of such side effects included diarrhea, vomiting, fatigue, fever and elevated liver enzyme levels, as well as increased sleepiness. These events led more patients who were taking cannabidiol to drop out of the study compared with those receiving placebo.

Of note, 5% of patients who were treated with cannabidiol became seizure-free, compared with none of the patients in the placebo group.

While the study was relatively small, the results are quite encouraging, and argue for larger prospective trials of cannabidiol to study its role as a potential replacement or adjunct for standard management of seizures in adults as well as children.

With this promising trial in Dravet syndrome, and two additional phase 3 trials in another severe and quite rare from of epilepsy known as Lennox-Gastatut syndrome, GW Pharma is on the brink of FDA submission for both indications before the end of 2017.

One concern with GW Pharma’s upcoming submission centers around an interaction of Epidiolex with clobazam, another popular drug to treat epilepsy, potentially leading to elevated levels of clobazam in the blood stream. Reducing the dose of clobazam may be one way to assure safety without sacrificing efficacy. Elevated liver enzymes may be an additional concern but are generally limited to patients already taking valproic acid, which can cause liver damage.

“This study highlights the clinically beneficial effects of a plant derivative that has been unjustly vilified like “fake news” and severely understudied for nearly 100 years,” said Rich Able, an advisory board member for Mobius Beverage Corporation, based in Bellevue, Washington. “In a time of major opiate abuse and pharmaceutical mismanagement of chronic conditions like pain and PTSD, cannabis may hold the key to helping clinicians manage an aging baby boomer population that can ill afford to continue consuming harmful synthetics and highly addictive opiate-based drugs.”