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Jul 12

FDA Approval of Epidiolex and the Cannabis-Based Drug Pipeline

By: Kristen Biernat, Cato Research

 

The Food and Drug Administration (FDA) granted approval of the cannabis-based drug Epidiolex to GW Research Ltd. (GW) on June 25, 2018.1 The FDA’s approval of Epidiolex represents two major milestones for GW:

First, it is addresses the unmet need for patients with Lennox-Gastaut syndrome and Dravet syndrome, two rare epilepsy disorders. The application received Orphan Drug designation for both indications and Fast-Track Designation for Dravet syndrome. Notably, Epidiolex is the first drug to be approved for the treatment of Dravet syndrome, a genetic disorder that appears during the first year of a child’s life and is associated with severe, fever-related seizures.

Second, it is the first FDA-approved prescription medicine that contains a purified compound derived from marijuana. Epidiolex is an oral solution that contains cannabidiol (CBD), one of over 60 compounds called cannabinoids found in the Cannabis plant.2 Unlike tetrahydrocannabinol (THC), which is also a cannabinoid, CBD does not cause euphoria or a “high”. The exact mechanism by which CBD produces its anticonvulsant effects is still under investigation.3

While Epidiolex is the first FDA-approved drug directly derived from cannabis, it is not the first cannabis-based drug that has been approved in the United States. To better understand how these products relate to each other, three categories may be employed:

  1. Drugs containing cannabinoids derived directly from cannabis
  2. Drugs containing synthetic versions of cannabinoids found in cannabis
  3. Drugs containing compounds that are similar to cannabinoids found in cannabis

As stated above, Epidiolex falls into the first category. However, the commercially available drugs Marinol, Syndros, and Cesamet fall into the second and third categories. Marinol and Syndros contain dronabinol, synthetic THC, and Cesamet contains nabilone, a synthetic analog of THC. All three compounds are indicated in adults for the treatment of nausea and vomiting associated with chemotherapy, while Marinol and Syndros are also indicated for the treatment of anorexia in individuals with AIDS.

The recent Epidiolex decision paves the way for the development of other cannabis-based drugs that fall into all three categories, but in particular, it sets a precedent for the development of drugs derived directly from the cannabis plant. Indeed, GW is also conducting Phase III trials with Sativex for the treatment of multiple sclerosis spasticity. Like Epidiolex, Sativex is an extract of the cannabis plant that contains cannabinoids (THC and CBD in a 1:1 ratio).4

There are also several drugs currently in development that contain synthetic cannabinoids as well as synthetic cannabinoid analogs. Zynerba Pharmaceuticals is conducting Phase II trials with a gel formulation for the transdermal delivery of CBD to treat neuropsychiatric disorders, such as Fragile X Syndrome. A THC pro-drug patch is also undergoing clinical trials for the treatment of Tourette Syndrome. In addition, Corbus Pharmaceuticals is currently conducting Phase II trials with Lenabasum (ajulemic acid), a THC-mimetic drug, for the treatment of rare inflammatory diseases, such as systemic sclerosis, cystic fibrosis, and dermatomyotisis.

Although Epidiolex has been approved by the FDA, it may not be marketed in the U.S. until it is rescheduled by the Drug Enforcement Agency (DEA). The DEA classifies drugs and substances into five schedules based on the drug’s medical use and abuse potential. Schedule I is the most restrictive and consists of drugs with no currently accepted medical use and a high potential for abuse, such as LSD, ecstasy, and cannabis. Schedule V is the least restrictive and consists of drugs with the lowest potential for abuse, such as cough preparations with less than 200 mg of codeine per 100 mL. CBD, a cannabis-derived compound, is currently classified as Schedule I, meaning that it cannot be sold for medical use. Removal of CBD from Schedule I is expected to take place within 90 days of FDA’s approval of Epidiolex, and while it is likely to remain a controlled substance, it is expected to be available for medical use this fall.5 However, removal of Epidiolex from Schedule I does not mean cannabis itself will also be reclassified. Indeed, cannabis was not rescheduled when Cesamet, Marinol, and Syndros, which all contain synthetic versions of THC, were classified as Schedule II, Schedule III, and Schedule II, respectively.6

In summary, the FDA-approval of Epidiolex indicates a promising future for cannabis-based drugs for the treatment of a range of disease states. While there are several products in the cannabis-based drug pipeline, drugs containing compounds derived from the cannabis plant may benefit most from the recent Epidiolex decision.

 

References:

  1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy”. The U.S. Food & Drug Administration. 25 June 2018.
  2. Atakan, Z. (2012) Cannabis, a complex plant: different compound and different effects on individuals”. Therapeutic Advances in Psychopharmacology. 2: 241-254
  3. “Mechanism of Action”. GW Pharmaceuticals.
  4. “Sativex (delta-9-tetrahydrocannibinol and cannabidiol in the EU) (nabiximols in the USA”. GW Pharmaceuticals.
  5. “Biosciences Announce FDA Approval of EPIDIOLEX® (cannabidiol) oral solution – the First Plant-derived Cannabinoid Prescription Medicine”.GW Pharmaceuticals.
  6. “Controlled Substances by DEA Drug Code Number”. 28 March 2018.

 

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