Some lawyers specializing in federal regulatory matters anticipate GW Pharmaceuticals plc will pressure FDA to move against the supplement industry if and once the British company obtains approval to commercialize its drug, Epidiolex.
Editor’s note: This is the second in a series of articles examining regulatory hurdles facing CBD producers and marketers in the dietary supplement industry, and ongoing efforts to comply with federal regulations.
Marketers and manufacturers of a dietary supplement ingredient in the United States may be running out of time before federal regulators intervene to protect a drug that is currently under investigation to treat severe forms of epilepsy.
Some lawyers specializing in federal regulatory matters anticipate GW Pharmaceuticals plc will pressure FDA to move against the supplement industry if and once the British company obtains approval to commercialize its drug, Epidiolex.
The reason?
FDA has proclaimed cannabidiol (CBD) isn’t a dietary supplement ingredient at all, thanks largely to GW’s current drug trials and a related exclusionary clause in the 1994 Dietary Supplement Health and Education Act (DSHEA).
“I think the market will stand as it is until GW has a commercially viable product, at which point FDA will start sampling at the border, and they will shut down the trade," said Marc Ullman, a New York-based attorney who is of counsel to Rivkin Radler LLP, in a phone interview.
Stephen Schultz, vice president of investor relations with GW (NASDAQ: GWPH), said his employer has been working on developing CBD for at least seven years since the company commenced pre-clinical work on cannabinoids, which are found in the cannabis plant.
In 2016, GW completed three Phase 3 studies of its CBD drug Epidiolex, for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. “All three of these trials were statistically significant for the primary endpoints of the trials," Schultz said in a phone interview.
In the first Phase 3 trial for the treatment of Lennox-Gastaut syndrome, a rare form of epilepsy that begins in young children and is difficult to treat, patients taking Epidiolex during the 14-week treatment period achieved a median reduction in monthly drop seizures of 44 percent, the company announced last summer in a news release.
The results compared to a reduction of 22 percent in patients who were administered the placebo, GW noted. On average, the trial participants were taking three anti-epileptic drugs and had previously tried an average of six other medicines that were ineffective, the release indicated.
London-based GW anticipates submitting a new drug application to FDA in the first half of 2017. Todd Harrison, a lawyer in Washington who advises clients on FDA regulations, expects GW to pressure FDA, demanding removal of supplements containing CBD, if Epidiolex is approved.
“If I’m GW … I’m going to be knocking on their door, saying … ‘Why aren’t you getting these CBD products off the market? I’ve spent hundreds of millions of dollars getting a drug approved, and you’re letting these supplement companies market’" an ingredient that wasn’t available in the food supply before GW commenced its drug trials, said Harrison, a partner with Venable LLP, in a phone interview.
On a question and answer webpage, FDA asserted cannabidiol products are excluded from the definition of a dietary supplement under the Federal Food, Drug & Cosmetic Act (FDCA), as amended by DSHEA.
The agency reasoned CBD has been authorized for investigation as a new drug, substantial clinical investigations have been instituted, and the investigations have been made public. FDA referenced GW’s clinical investigations of Epidiolex and Sativex, a separate drug that contains CBD and THC, the psychoactive ingredient in marijuana.
Despite FDA’s legal opinion, myriad CBD products that are described as supplements—and therefore not subject to premarket drug approval—have sprung up on the U.S. market and are continuing to be widely sold.
Some lawyers contend FDA’s position is erroneous. Garrett Graff, an associate in Denver with the Hoban Law Group, which specializes in cannabis law and has challenged a marijuana extract rule affecting CBD that was published by the Drug Enforcement Administration (DEA), argued an exception in DSHEA to the exclusionary clause applies to CBD.
“Hemp oil and cannabinoid-rich hemp oil, along with CBD specifically, was marketed prior to the GW Pharma application," he said in a podcast interview with Natural Products INSIDER.
The lawyer also disputed other aspects of FDA’s conclusions.
“While the FDA claims that they have made public the substantial clinical investigations that they’ve conducted, according to the GW Pharma application, we … respectfully disagree with that conclusion and do not believe that those results, and the substantial nature of them, have been conducted and/or disclosed," Graff declared.
While GW’s Schultz declined to comment specifically on FDA’s opinion that CBD cannot be sold in a dietary supplement, he maintained patients who suffer from severe forms of epilepsy need a drug that is consistent with the “hallmarks of a medicine."
“And those hallmarks are that it doesn’t vary, it’s exactly the same every time the patient takes it, [and] that it’s fully described for how it performs both on the safety and efficacy standpoint against a placebo," he said, “so you know what it does and what it doesn’t do."
Most of the products marketed as CBD oils fail to carry such hallmarks, Schultz said, “and never will." In fact, he noted FDA tested several CBD products and discovered some didn’t even contain any cannabinoids.
“So now you have a very desperate patient population and companies … taking advantage of that," he said. “That’s a problem, and the FDA was established to protect the consumer, and that’s exactly what they’re doing."
The agency, nonetheless, hasn’t moved to shut down the CBD industry, or even specific manufacturers or marketers. In 2015 and 2016, FDA issued warning letters to a select number of companies, but industry lawyers said regulators were focused largely on impermissible claims that the products could treat diseases. The most recent letters were issued in February 2016.
“If you make crazy drug claims, it’s an invitation for FDA to enforce against you no matter what you’re marketing," said Ullman, the regulatory lawyer.
FDA declined to specifically comment on whether it would move to take enforcement action against CBD marketers if GW obtains drug approval for Epidiolex. GW also declined to comment on whether it would ask the agency to target companies.
“When a product is in violation of the FD&C, the FDA considers many factors in deciding whether or not to initiate an enforcement action," Michael Felberbaum, an FDA spokesman, said in an emailed statement. “Those factors include, among other things, agency resources and the threat to the public health. The FDA also may consult with its federal and state partners in making decisions about whether to initiate a federal enforcement action."
Pharmanex v. FDA: Red Yeast Rice
The pharmaceutical and supplement industries have butted heads before. FDA is likely to lean on court precedent involving red yeast rice, should regulators end up in court with the CBD trade.
In 1987, Merck obtained FDA approval for its drug Mevacor for the treatment of high cholesterol and heart disease. Lovastatin is the active ingredient in the drug.
“Companies then started marketing red yeast rice for lovastatin content," Ullman recalled, “and FDA said, ‘Hold on. Lovastatin is an approved drug. You can’t sell lovastatin as a dietary supplement, nor can you manipulate your red yeast rice for lovastatin content.’"
On Sept. 30, 1997, FDA informed Pharmanex Inc.’s lawyer that the company’s red yeast rice product, Cholestin, was an unapproved new drug and not a dietary supplement, according to a petition the company filed with FDA the following month.
FDA interpreted the FDCA as prohibiting any supplement that contains lovastatin as a constituent, the petition noted. FDA concluded Pharmanex failed to establish lovastatin was marketed as a food or supplement before the approval of Merck’s drug.
Pharmanex’s petition described Cholestin as a “natural dietary supplement composed entirely of red yeast rice made by the traditional Chinese method."