Medical Cannabis Special Feature: Beyond Medical Marijuana
Although the endocannabinoid system has been intensely studied, there are still few drugs approved or in development that interact with it.
By Christiane Truelove • [email protected]
A potentially large market is starting to coalesce around the endocannabinoid pharmaceutical market – and it isn’t due to the makers of CBD oil for wellness purposes.
Even as more states are approving medical marijuana and dispensaries have boomed during the pandemic, the lack of clinical data around “natural” CBD and other plant-derived compounds – along with the federal government’s statutory disapproval of any product that can get a user high – means that the companies who want to advance drugs that work with the endocannabinoid system have a difficult scientific road ahead of them. They must formulate drugs that can target the receptors that trigger the “good” effects without triggering the bad (see Q&A with Yuval Cohen, CEO of Corbus Pharmaceuticals Holdings, for an explanation of the endocannabinoid system and what it does).
Creating these drugs is difficult – but not impossible. GW Pharmaceuticals managed to strike gold from the green with the U.S. approval of Epidiolex in June 2018 for severe forms of epilepsy. The drug is the first plant-derived cannabinoid prescription medicine and the only FDA-approved form of cannabidiol (CBD). Epidiolex was initially approved by the FDA in June 2018 for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older. In July 2020, the FDA approved the product for the treatment of seizures associated with tuberous sclerosis complex (THC) in patients 1 year of age and older.
While Epidiolex contains CBD, it does not contain the compound that can get users high, THC. The drug achieved sales of more than $500 million during 2020.
“Epidiolex sales increased by over 70 percent in 2020 despite the challenges of COVID-19, reflecting the positive impact this medicine has on patients as well as the performance of our commercial team,” stated Justin Grover, GW’s CEO, in January. “We remain encouraged by our patients’ experience on this product, as demonstrated by high persistence and refill rates. This, combined with our expansion of payer coverage and the recently approved tuberous sclerosis complex indication, leads us to expect continued strong growth in 2021 in both the U.S. and Europe.”
GW has been seeking FDA approval for a second cannabis-derived product, Sativex (nabixomols), for the treatment of spasticity due to multiple sclerosis. Unlike Epidiolex, Sativex contains THC in addition to CBD, as well as minor cannabinoids and other non-cannabinoid components. Phase III trials for Sativex are under way in the United States, with results expected later in 2021.
GW’s success made it the subject of an acquisition. The company became part of Jazz Pharmaceuticals during May 2021. “The addition of GW further diversifies our commercial portfolio and innovative pipeline with therapies that are complementary to our existing business, including Epidiolex, a high-growth commercial product with near-term blockbuster potential,” says Bruce Cozadd, chairman and CEO of Jazz.
Unlike GW/Jazz, other companies are opting to head down the synthetic route rather than naturally derived route, with lab-created versions of CBD and THC. The grandaddy of these drugs is Marinol (dronabinol), approved in 1985 for treating anorexia associated with weight loss in patients with AIDS, and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
Other companies are choosing to go a different route all together by creating small-molecule drugs that target specific endocannabinoid receptors. Two companies – Corbus and Emerald Health Pharmaceuticals – have drugs in development for indications such as dermatomyositis, systemic sclerosis, obesity, and cancer (see chart for more info).
Corbus’ lead drug is lenabasum, an oral, non-immunosuppressive preferential cannabinoid-2 agonist. The drug failed the primary endpoint of its Phase III trial for systemic sclerosis in September 2020. Dr. Cohen is not discouraged, however, telling Med Ad News that lenabasum did show some effect and the company will be discussing the results with FDA and determining next steps.