Epidiolex Approved by the FDA for Epilepsy

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Epidiolex Approved by FDA

Monday, June 25th, U.S. Food & Drug Administration (FDA) approved EPIDIOLEX®(cannabidiol) oral solution for the treatment of seizures associated with two severe epilepsy syndromes known as Lennox-Gastaut syndrome and Dravet syndrome in patients two years of age or older. For those living with intractable seizures caused by Lennox-Gastaut syndrome and Dravet syndrome, EPIDIOLEX represents a significant medical advancement.

For the Hypothalamic Hamartoma (HH) community, these results are encouraging as well. While not tested for efficacy on gelastic seizures, it has been reported by HH clinicians that as much as 14% of the HH patient population may also develop Lennox-Gastaut syndrome. (1)

Lennox-Gastaut syndrome is a rare and often debilitating form of childhood-onset epilepsy that is highly treatment-resistant. It is characterized by multiple seizure types, moderate to severe cognitive impairment and an abnormal EEG with specific general slow spike-and-wave discharges. LGS typically appears between the second and sixth year of life. This translates to a prevalence of approximately 12,500 children under the age of 18 in the United States and between 39,000 - 48,000 children and adults in the U.S. (2)

Dravet syndrome is a rare and catastrophic form of intractable epilepsy that begins in infancy and is highly treatment-resistant. Previously known as Severe Myoclonic Epilepsy of Infancy (SMEI), it affects 1:15,700 individuals, 80% of whom have a mutation in their SCN1A gene. (3)

The FDA approval of EPIDIOLEX will soon bring to market the first drug derived from the cannabis plant in the U.S. However, launch of the product may be delayed until late 2018 as the Drug Enforcement Agency (DEA) must reschedule Epidiolex from its current Schedule 1 status. Schedule 1 drugs are ones the DEA deems to have no medicinal use and a high potential for abuse.

Recently, double-blind, placebo-controlled studies that have been conducted were presented at major scientific meetings and in press releases by GW Pharmaceuticals. (See the CBS News story)

Results of those studies include:

Studies involving 214 people who received Epidiolex (99% CBD) in an open-label study (without a placebo control) and who completed 12 weeks or more on the drug were published in Lancet Neurology (4)

  • People who received Epidiolex ranged from 2 to 26 years old with an average age of 11.
  • All had epilepsy that did not respond to currently available treatments.
  • During the study, seizures decreased by an average of 54%.
  • People taking the anti-seizure medication clobazam (Onfi) seemed to have a better response when compared to those that were not on this medication.

In addition, two additional studies using Epidiolex for LGS in children and adults and one with children who have Dravet syndrome showed promising results.

  • Drop seizures were reduced in the two LGS studies by over 40% compared to less than 20% for people who got the placebo, which was statistically significant.
  • In the Dravet study, approximately 40% reduction in convulsive seizures was noted compared to 17% reduction for the placebo group. Again, significance was found compared to the placebo group.

Some of the most common side effects included:

  • Side effects that occurred in 10% or more of people included
    • sleepiness (21%)
    • diarrhea (17%)
    • fatigue (17%)
    • decreased appetite (16%)
  • Most side effects were described as mild or moderate and went away.
  • Serious side effects happened in 52 people
    • 22 of these were possibly related to the drug
    • The most common serious possible side effect was status epilepticus, when a person has long or repeated seizures

The safety data from the trials in people with Lennox Gastaut syndrome and Dravet syndrome showed similar side effects in that tiredness, diarrhea, and upset stomach feeling are reported the most. Interestingly, people getting the placebo report lots of diarrhea and upset stomach feeling as well. This may be due to both products being oil.

There are drug-to-drug interactions that are being identified with these studies of CBD in epilepsy syndromes.

  • It appears that people who had increases in their liver enzymes to a level three times or more than normal were also on valproic acid (VPA), a commonly used anti-seizure medication. The levels of VPA were not increased when taken with CBD. Therefore, it is thought that as VPA is broken down, one of its parts may interact with CBD, thus putting some people at increased risk for liver issues.
  • Also, as clobazam (Onfi) is broken down, its major part appears to interact with CBD in some people and may be the cause of tiredness that is seen with some people who are on CBD and Onfi.
  • More work in this area is needed to fully understand these drug to drug interactions.

While treatments are promising, it is worth noting that there are still conflicting laws regulating medical marijuana.

A number of states in the U.S. have laws allowing cannabis to be recommended and dispensed to people for medical reasons. However, this does conflict with federal laws and there are further complications for research on cannabis due to federal restrictions. This can mean physicians who choose to follow the state laws on medical use of marijuana could be breaking a federal law.

Some states have acted to include protections for physicians, but they must be aware of both federal and state laws and the potential implications. A clearer understanding of the laws governing this issue is needed.

It is also illegal for parents to carry medical cannabis across state lines or have products shipped to them. Companies will often label CBD projects as hemp extract to skirt laws. However, if the product has CBD in it, then it is a Schedule I substance and it is illegal to ship it across state lines. If you want to know more about the legal issues associated with the medical marijuana laws, the National Conference of State Legislatures has comprehensive information.

Hope for HH will continue to follow the outcomes of other rare epilepsy patients using Epidiolex, or any other CBD based product, and let you know of any upcoming trials for hypothalamic hamartoma patients.

References:

(1) Textbook of Epilepsy Surgery – Chapter 41, Hypothalamic Hamartomas by AS Harvey, pgs. 354-359.

(2) Trevathan et al. Prevalance and descriptive epidemiology of Lennox-Gastaut syndrome amont Atlanta children. Epilepsia. Dec 1997

(3) Wu, E., et. al. (2015). Incidence of Dravet Syndrome in a US Population. Pediatrics 136(5): 1310-e1315. doi: 10.1542/peds.2015-1807.

(4) Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet neurology 2015.

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