FDA’s Approval of First Cannabis-Derived Drug Breaks New Ground, Met with Mixed Reactions

Last week, the Food and Drug Administration approved the first cannabis-derived drug, Epidiolex®, for the treatment of two rare forms of epilepsy.

This approval follows an FDA Advisory Committee’s unanimous recommendation in April to approve Epidiolex based on clinical trials that demonstrated the drug’s efficacy in reducing otherwise uncontrollable daily seizures. The approval has been viewed favorably by pharmaceutical manufacturers that can see an FDA approval pathway for cannabis-derived drugs crystalizing. At the same time, some players in the cannabis industry perceive FDA’s blessing of a cannabis-derived drug as a new hurdle for their business, particularly when marketing their own cannabis products.

Epidiolex is an oral solution with a purified cannabis-derived active ingredient, cannabidiol. Despite FDA’s recent approval, Epidiolex cannot be sold in the United States because CBD is currently a Schedule I substance under the federal Controlled Substances Act. By definition, Schedule I substances are considered to have a high risk of abuse potential and no currently-accepted medical use in the United States. However, FDA’s approval indicates that CBD does indeed have an accepted medical use—treatment of certain forms of epilepsy. Therefore, in order to comply with the CSA, CBD must be removed from Schedule I by the Drug Enforcement Administration. In its letter approving Epidiolex (available here), FDA noted that it had already submitted a scheduling recommendation to DEA. By statute, DEA has 90 days from the approval date (June 25) to issue a scheduling decision, though the entire scheduling process can take much longer.

How strictly DEA will decide to control CBD will turn on its conclusions regarding CBD’s abuse potential. Although FDA’s scheduling recommendation will not be publically available before DEA renders its decision, FDA appears to have concluded that “CBD does not appear to have abuse potential.” (See the FDA Briefing Document prepared for the April Advisory Committee meeting.) Yet even if FDA recommended rescheduling all CBD, as opposed to only the CBD in Epidiolex, or removing CBD from federal control entirely, DEA is not obligated to follow FDA’s recommendation. Indeed, DEA has declined to follow FDA’s scheduling recommendations in the past. For example, when FDA approved Marinol, the first FDA-approved drug containing synthetic THC (dronabinol), FDA recommended that all forms of dronabinol be rescheduled from Schedule I to Schedule II. DEA declined to do so and instead opted to re-schedule the substance very narrowly by placing only “synthetic dronabinol in sesame oil and encapsulated in soft gelatin capsules” on Schedule II.

Further, even if DEA were to completely de-schedule CBD, current and future FDA-regulated products containing CBD would still need to comply with the requirements of the Food, Drug, and Cosmetic Act (“FD&C Act”). FDA emphasized this point via an update to its webpage FDA and Marijuana: Questions and Answers that was made the same day Epidiolex was approved. FDA added a Q&A regarding industrial hemp grown in accordance with the Farm Bill (which is exempt from the CSA):

23. What is the effect of section 7606 of the Agricultural Act of 2014 (sometimes known as the “industrial hemp” provision of the Farm Bill) on the FD&C Act?

 

A: As stated in the Statement of Principles on Industrial Hemp (81 FR 53395, Aug. 12, 2016), section 7606 did not amend the FD&C Act. For example, section 7606 did not alter the approval process for new drug applications, the requirements for the conduct of clinical or nonclinical research, the oversight of marketing claims, or any other authorities of the FDA as they are set forth in that Act. All products must comply with any relevant provisions of the FD&C Act.

Given the timing of this addition, FDA likely added this statement to emphasize the point that even if CBD is derived from sources that are legal under the CSA, it cannot lawfully be added to food or dietary supplements under the FD&C Act until completion of the appropriate regulatory process.

FDA’s approval signals an approved medical use and pathway to market for certain cannabis-derived products. Many in the pharmaceutical industry look forward to DEA’s potential rescheduling of CBD to assess new opportunities in the wake of the Epidiolex approval. Not everyone shares the same enthusiasm, however, as FDA’s action presents incidental challenges for the medical use cannabis market.

While some believe FDA’s approval will lend legitimacy to medical use cannabis businesses that are largely state-regulated, these same businesses may feel pressure to seek FDA approval for certain indications. Before Epidiolex, no clear pathway to market for cannabis-derived drugs existed and investors, business partners, and patients may have agreed that FDA approval was too infeasible to pursue. This has now changed. Epidiolex provided a blueprint for an approval from FDA that is no longer speculative and may set a new bar for medical claims made by the cannabis industry.

In addition, FDA has thus far exercised limited enforcement resources to target companies marketing CBD products. Now, FDA prepares to regulate the marketing of at least one cannabis-derived drug. As further cannabis-derived drugs are approved, FDA’s enforcement posture regarding medical use cannabis could evolve. In FDA’s announcement about Epidiolex’s approval, Commissioner Gottlieb described the agency’s willingness to take enforcement action:

[W]e are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.

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