The First Cannabis-Derived Drug Heads for FDA Approval

EpidiolexA new treatment for two particularly severe forms of epilepsy is on track to become the first cannabis-derived drug to gain approval from the U.S. Food and Drug Administration (FDA). On April 19, an FDA advisory panel unanimously recommended the approval of Epidiolex (cannabidiol, also known as CBD), under development by British pharmaceutical company GW Pharmaceuticals for the treatment of Lennox-Gastaut and Dravet syndromes. Both conditions affect young children, often subjecting them daily to large numbers of seizures, which can be strong enough to break bones. Those affected are at high risk of intellectual and developmental disabilities, as well as premature death before the age of 20.  

 

The FDA brief to the advisory panel strongly supported the GW application, saying that the company had submitted “positive results of efficacy from three randomized, double-blind, placebo-controlled trials in patients with both conditions.” Trial results showed a 40% reduction in seizure rate, with some patients experiencing a decrease in seizures from 40-50 per day to a few or even none per week. While the agency also cited the risk of a potentially serious side-effect (liver injury), reviewers felt that this risk could be managed by tracking liver function during treatment with the drug, and thus concluded that the drug’s benefit greatly outweighs the risk.

 

Epidiolex is therefore likely to be approved before the end of June as the first cannabis-based drug for epilepsy and the first treatment for Dravet syndrome (there are six approved drugs for Lennox-Gastaut syndrome, but they offer limited benefit compared to Epidiolex). While synthetic versions of tetrahydrocannabinol (THC, the other well-known chemical in cannabis) such as Marinol, Syndros, and Cesamet are currently used to treat nausea associated with chemotherapy and to help AIDS patients avoid weight loss, Epidiolex is poised to become the first FDA-approved cannabis-derived drug to be produced from the plant. GW extracts CBD from its own proprietary strain of cannabis, which is bred for high CBD content and low THC content.  Unlike THC, CBD is non-psychoactive, meaning it does not elicit a “high.” GW also manufactures Sativex, a mouth spray of formulated cannabis extract (both THC and CBD) that is commercialized outside the United States to alleviate spasticity and other symptoms in multiple sclerosis.

 

The epilepsy community has hailed the FDA Advisory Committee’s vote. Some families with children affected by the two conditions had moved to states with legal medical marijuana to gain access, but having an approved drug in a standard dosage form is an important advance. Medical marijuana usage presents risks from irregular dosing, inconsistent and low-quality supplies, and the risk of side effects without medical oversight, and these risks will likely be mitigated with the introduction of a regulated drug.

 

Still unknown is the consequence that an FDA approval will have on research looking at other medical effects of cannabis, or on the plant’s listing and regulation by the Drug Enforcement Agency (DEA) as a “Controlled Substance” with “no medical value.”  GW reportedly had to go through a complicated bureaucratic process to conduct their studies, including a special license from the DEA and specialized equipment.

 

Will the DEA need to reschedule CBD — if not the cannabis plant itself — now that medical value has been clearly shown for this chemical? Will the FDA approval open the door to removing at least some restrictions on research into the medical effects of cannabis? And will the FDA decision affect the outcome of the EMA marketing authorization review for Epidiolex (expected in Q1 2019)? If approved, will Epidiolex have a smooth market access route, or will it hit the same bumpy road that Sativex experienced in France where the manufacturer and the French Health Authorities have not yet reached a pricing agreement?