A new study shows a mean reduction in seizures of over 50% in 3 months among some patients with epilepsy taking cannabidiol (CBD).
Results of an open-label, multicenter trial of a liquid product that is 99% cannabidiol (Epidiolex; GW Pharmaceuticals), the major nonpsychoactive ingredient in marijuana, showed that treatment provided seizure relief in children with Dravet syndrome and Lennox-Gastaut syndrome (LGS) who had been resistant to at least eight antiepileptic drugs.
"I think this is an important study," and it's "definitely the largest" study of a pure medical marijuana product, commented lead investigator Orrin Devinsky, MD, director, New York University (NYU) Epilepsy Center, and professor, neurology, NYU. "It looks very, very promising but until we get blinded data, we have to be humble," he said.
The full results will be presented next week during the American Academy of Neurology (AAN) 67th Annual Meeting.
CBD is a component of Cannabis sativa with anticonvulsant activity in preclinical models of epilepsy, independent of activity at known endogenous cannabinoid receptors, the authors write. Ten centers have independent US Food and Drug Administration (FDA)–approved open-label Expanded Access Programs and have treated children and young adults with treatment-resistant epilepsies using pure CBD.
Data have been collected on demographic characteristics, seizure counts, and safety through case report forms and tabulated in this series of open-label trials, the authors note. Eligibility was determined and documented in protocols specific to each site after FDA and institutional review board review.
This new analysis included patients aged 2 to 26 years (mean age, about 10.5 years) with uncontrolled seizures enrolled at NYU, Children's Hospital of Philadelphia (CHOP), and eight other centers across the United States. Patients with Dravet syndrome and LGS represented two of the larger epilepsy groups, although the study also included patients with over 10 other conditions, some genetically related.
Study patients had tried an average of more than eight antiseizure medications and experienced an average of two seizures per day.
The children took CBD in liquid form in a daily dose titrated up to 25 mg per kg.
Data were collected on 213 patients with treatment-resistant epilepsies for safety evaluation. One hundred twenty-three patients had at least 12 weeks of continuous exposure and were included in efficacy calculations.
At month 3, the median percentage reduction in total seizures (convulsive and nonconvulsive) among 123 patients was 48% and the responder rate (50% or greater reduction) was 48%. Seizure freedom was seen in 10% of these patients.
In 93 patients with month 4 data, the median percentage reduction in seizures was 52% and the responder rate was 52%.
In patients with Dravet syndrome (n = 23), the median percentage reduction for all convulsive seizures at 3 months was 51% and the responder rate was 55%. For patients with LGS (n = 10), the median percentage reduction in atonic seizures at 3 months was 52% and the responder rate was 50%.
"The treatment was very effective in this group of children who were extremely drug resistant" and so were "not your average group of customers, so to speak," said Dr Devinsky. The patient's age didn't make a difference to the response rate, he said.
Although patients with Dravet syndrome did slightly better than the others, "I think it's too early to say how significant that finding will be," said Dr Devinsky. The treatment seemed to work for all seizure types that researchers looked at, "but we will need more randomized blinded data to sort that out," he added.
Nine patients with a "mix" of different conditions discontinued the treatment because of adverse events, said Dr Devinsky. The most common adverse effects were somnolence (21%), diarrhea (17%), fatigue (17%), and decreased appetite (16%).
Some of the adverse effects could have been related to drug interactions. "The patients were on an average of three drugs before they started the new drug, so it's not a surprise that some of them became very tired on a combination of four drugs," said Dr Devinsky.
The "key caveat," however, is that this was an open-label study, he said. "It's not a randomized controlled trial so we have no idea what the placebo number was — was it 10%; was it 20% ; was it north of 20%? If its 10%, this was an incredibly positive finding; if it's 30% it was obviously much less dramatic."
A double-blind study of the drug in patients with Dravet syndrome in multiple centers in the United States and Europe has already gotten under way, and a similar study in patients with LGS is about to begin. "Based on those studies, the company will hopefully try to seek approval from the FDA," said Dr Devinsky.
Asked to comment, epilepsy expert Elson So, MD, professor, neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, said one of the strengths of the study was that it used a pharmaceutical-grade CBD instead of artisanal CBD. "Pharmaceutically produced CBD gives greater assurance of reliable and known CBD amount used and assessed, whereas it has been shown that artisanal CBD varies greatly in the amount of CBD that is actually present."
Despite some limitations — for example, being nonblinded, and having small numbers of patients with Dravet syndrome and LGS — Dr So said he found the study encouraging.
"The rate of seizure freedom associated with the use of Epidiolex in this study appears to be lower than what is expected from anecdotal experience with CBD, but the rates do appear to be higher than what had been reported for many approved antiepileptic medications."
However, he added, the results "offer only a preliminary glimpse" of the potential usefulness of CBD in epilepsy. "It would be premature to conclude from the results of this study that CBD is superior or equivalent to established therapies for seizures and epilepsy."
The American Epilepsy Society issued a statement commenting on the new results. The society, they write, "has long been supportive of formal trials like the one conducted by Dr Devinsky for GW Pharmaceuticals, where a pharmacy-grade, purified and uniform preparation of cannabidiol (CBD) is being administered under the guidance and close monitoring of an epilepsy professional. This is the first formal clinical study to be undertaken on any marijuana extract in the US and this is a critical first step in helping shed light on the potential role CBD may have in the treatment of epilepsy."
They note that this trial uses "a vastly difference substance" than products used in Colorado and other states. "In most cases, the families and children who have been using CBD oils outside of this study, have been receiving highly variable artisanal preparations with unverified levels of cannabis oil.
This has resulted in many different outcomes from those presented in Dr. Devinsky's study," the AES writes.
These results pave the way for proceeding to phase 3 placebo controlled studies to determine the safety and efficacy of this product, they add. "Like many, AES is hopeful that promising new therapies will be developed to provide answers for many people with epilepsy and their families who live with uncontrolled seizures.
"AES calls for investment in more controlled clinical trials for promising new therapies in appropriate and controlled circumstances," the society concludes. "Scientific studies help the entire epilepsy community to understand how and why various treatments work and for whom they are effective. Research also helps us understand the correct dose, side effects, and potential interactions with other medications. At present, the epilepsy community does not know if marijuana is a safe and effective treatment nor do we know the long-term effects that marijuana will have on learning, memory and behavior, especially in infants and young children. Studies like the one presented at the AAN meeting help increase our understanding but much more is needed."
The study was supported by GW Pharmaceuticals. Dr Devinsky and Dr So have disclosed no relevant financial relationships.
American Academy of Neurology (AAN) 67th Annual Meeting. Washington, DC. Abstract 9222. To be presented Wednesday, April 22, 2015.
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