(Gerd Altmann, Pixabay)
17 May 2018. A clinical trial shows treatments made with cannabidiol, a medical-grade derivative of cannabis plants, reduce the number of severe seizures in people with Lennox–Gastaut syndrome, when combined with conventional drugs. Results of the late-stage trial, including reports of widespread adverse effects, appear in today’s issue of New England Journal of Medicine (paid subscription required).
Lennox-Gastaut syndrome is a rare, severe form of epilepsy marked by multiple types of seizures and intellectual disability. Seizures often begin in early childhood, and include tonic seizures where muscles stiffen uncontrollably, while other seizures can result in loss of consciousness or weak muscle tone, also known as drop seizures, causing falls and injuries. Almost all children with Lennox-Gastaut syndrome also develop learning problems and intellectual disabilities because of their frequent seizures.
Greenwich Biosciences in Carlsbad, California, a subsidiary of GW Pharmaceuticals in London, U.K., develops Epidiolex, an oral formulation of cannabidiol that the company says does not produce an emotional high associated with marijuana. Greenwich Biosciences and GW are developing Epidiolex for Lennox-Gastaut syndrome and other less frequent forms of epilepsy including Dravet syndrome and infantile spasms, with all applications in clinical trials or submitted to regulatory authorities for review.
The Lennox-Gastaut syndrome trial is a late-stage study, enrolling 225 patients at 30 sites in the U.S. and other countries. Participants, ranging in age from 2 to 55, were randomly assigned to receive their usual epilepsy medications, along with a high or low dose of Epidiolex, or a placebo. The drugs were taken twice a day for 14 weeks, preceded by a 4-week period to take baseline measurements, and ending with a 4-week safety check period. Dosage levels were calculated in terms of the weight of participants, since many were children.
The researchers, led by neurology and psychiatry professor Orrin Devinsky at New York University medical school, looked primarily at the number of drop seizures among participants per 28 days while taking Epidiolex or placebo, compared to the earlier baseline periods. The team also tracked other seizures and adverse effects while taking the drug.
The results show marked reductions in the number of drop seizures among Epidiolex recipients, but also widespread adverse effects. Drop seizures diminished by 42 percent among the high-dose Epidiolex recipients, while those receiving the lower dose experienced a 37 percent reduction. Placebo recipients reported 17 percent fewer drop seizures. The differences in drop seizures between Epidiolex and placebo recipients were large enough for statistical reliability.
Participants also reported high rates of adverse effects, particularly among high-dose Epidiolex recipients. While most adverse effects were rated mild or moderate, they included sleepiness, vomiting, diarrhea, fever, decreased appetite, and upper respiratory infection. Nearly all (94%) of the high-dose group reported these effects, but also 84 percent of low-dose recipients, and 7 in 10 (72%) of placebo recipients. Nearly all, 6 of 7, of those who discontinued participation in the trial were in the high-dose group, and 14 participants experienced elevated liver enzymes, which the researchers say are reversible.
GW Pharmaceuticals says preliminary results of the trial and findings from a similar study among patients with Dravet syndrome were already given to an advisory committee of FDA that on 18 April recommended supporting the company’s application. Final agency approval is expected by the end of June.
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