DEA Reschedules Epidiolex, Allowing Therapy to Enter US Market

Justin Gover, CEO of GW Pharmaceuticals

Justin Gover

Three months after its approval by the FDA, cannabidiol (Epidiolex, GW Pharmaceuticals) has been rescheduled to Schedule V, the lowest restriction classification, by the US Drug Enforcement Administration (DEA).

The company has stated that it plans to bring the drug to market in the United States in the next 6 weeks. Availability will be dependent mostly on the time involved in obtaining the required Schedule V licenses for the US distributor and importer. The medicine will be marketed in the United States by Greenwich Biosciences, the subsidiary of GW Pharmaceuticals.

The product label for the therapy will also now be finalized. It is the only cannabinoid-derived therapy approved for use in the US. It was approved to treat seizures caused by Dravet syndrome and Lennox-Gastaut syndrome (LGS) on June 25, 2018.

“We are pleased that the DEA has placed Epidiolex in the lowest restriction Schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said Justin Gover, GW’s chief executive officer, said in a statement. “With this final step in the regulatory process completed, we are working hard to make Epidiolex available within the next six weeks as we know there is excitement for a standardized version of cannabidiol that has undergone the rigor of controlled clinical trials and been approved by the FDA.”

The decision by the DEA was made based on the clinical and non-clinical data available for the therapy, which evaluated its potential for abuse. The decision to move it to Schedule V applies only to cannabidiol products approved by the FDA, and other non-approved cannabidiol therapies will remain Schedule I, according to the DEA. A number of commonly prescribed anti-epilepsy drugs, such as lacosamide (VIMPAT), brivaracetam (BRIVIACT), and pregabalin (Lyrica), remain Schedule V.

In a trial of patients with LGS, there was a ≥50% reduction in drop-seizure frequency for 39% of patients in the 20-mg group, 36% in the 10-mg arm, and for 14% with placebo. This decline represented a significant improvement with cannabidiol versus placebo for the 20-mg dose (odds ratio [OR], 3.85; P <.001) and the 10-mg dose (OR, 3.27; P = .003).²

In a separate study for Dravet syndrome,³ the median frequency of convulsive seizures per month declined by -6.5 from 12.4 at baseline for patients treated with cannabidiol. In the placebo group, seizures declined by just 0.8 from baseline. There were 43% of patients achieving a 50% reduction with cannabidiol compared with 27% with placebo (OR, 2.00; P = .08).

In a conversation with NeurologyLive, M. Scott Perry, MD, Medical Director of Neurology and Co-Director of the Jane and John Justin Neurosciences Center at Cook Children’s, said that “Epidiolex is a nice addition to the collection of drugs we have. As far as we know it’s a new mechanism of action, we’re not exactly sure how it works yet, but a new mechanism of action compared to the other drugs.”

“It works, I mean it’s not the most amazing drug in the world, not everyone is going to be seizure free on it, but it does reduce seizures,” he added.

Notably, he acknowledged that while it has a better tolerability profile than some of the other drugs, it’s not completely without adverse effects. In clinical trials, the most common adverse reactions that occurred in patients given Epidiolex were somnolence, decreased appetite, diarrhea, transaminase elevations, fatigue, malaise, and asthenia, rash, insomnia, sleep disorder and poor-quality sleep, and infections.

Ultimately, Perry commented that this is just the first step in a class that could be epically impactful. While it’s a solid step, he said that, really, it’s only a first step. “The cannabis plant has so many different substances in it, so many phytocannabinoids to look at besides CBD. There are potentially multiple other drugs within the plant that we’ll find over time that are potentially even more efficacious than the CBD itself,” he explained.

REFERENCES

1. GW Pharmaceuticals plc and its U.S. Subsidiary Greenwich Biosciences Announce the DEA has Rescheduled EPIDIOLEX® (cannabidiol) Oral Solution to Schedule V [press release]. London, UK; Carlsbad, CA: GW Pharma. Published September 27, 2018. http://ir.gwpharm.com/news-releases/news-release-details/gw-pharmaceuticals-plc-and-its-us-subsidiary-greenwich-0. Accessed September 27, 2018.

2. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox—Gastaut syndrome. N Engl J Med. 2018; 378:1888-1897

3. Devinsky O, Cross JH, Laux L, et al. Trial of Cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017; 376:2011-2020.