By Cliff Mintz, - Contributing Editor
The current U.S. legal/regulatory landscape has given rise to two distinct types of companies that are attempting to commercialize cannabis products. The first of these is commonly referred to as medical marijuana companies, or as Steven Schultz, VP of investor relations at GW Pharma suggested, “nutraceutical or herbal remedy companies that promote the medicinal properties of cannabis.”
Typically, products from these companies are botanical extracts or actual plant materials derived from specific cannabis strains with anecdotally-reported medicinal properties that can be topically applied, ingested, smoked, or vaporized. Patients require a prescription from a licensed physician to obtain medical marijuana, and it can be used only in states that permit consumption of cannabis for medical purposes. Interstate transport of medical marijuana (even between states with medical cannabis legislation in place) is prohibited by federal law.
Unlike medical marijuana companies, biopharmaceutical companies, including GW Pharma, Kannalife Sciences, Aphios, and others, are committed to developing cannabis-derived pharmaceuticals using conventional U.S. FDA regulatory approval pathways. “The idea behind our approach is to offer the market, and more importantly patients, a medicine that has been through a full regulatory review and is well characterized regarding efficacy, safety, and interactions with other drugs,” offered GW Pharma’s Schultz. He added, “None of those things are present in medical marijuana offerings.”
Likewise, Dean Petkanas, CEO of New York-based Kannalife Sciences, a phytomedical company that is developing cannabis-based drugs to treat hepatic encephalopathy and other neurological disorders, said, “Doctors want to know what they are prescribing to their patients and anecdotal evidence about the therapeutic benefits of a plant-based nutraceutical grown by ‘new-age-pot-farmer-wanna- be-pharmacists’ is simply not going to cut it. Also, added Petkanas, “In the case of some intractable diseases, there will be a need for extremely potent pharmaceutical cannabis-based products, which normally cannot be achieved using even the best plant-based extraction technologies.”
While the business case for developing pharmaceutical cannabis-based drugs is sound, the cost and time required for regulatory approval of these products will be much greater than those required for commercializing medical marijuana products. Put simply, medical marijuana products will be commercialized first and likely garner an early majority share of the rapidly emerging medical cannabis market. “Not to worry,” offered Trevor Castor, CEO of Boston-based Aphios Corp., a biopharmaceutical company developing cannabinoid-based products to treat emesis (nausea and vomiting), cachexia (wasting diseases), and CNS disorders like MS and Alzheimer’s disease, “the market is large enough to support both the nutraceutical/ herbal remedies and pharmaceutical sides of the business. They can easily coexist in today’s marketplace.” Further, by way of an example, Castor pointed out that the multibillion-dollar omega 3 fatty acids market comfortably supports the sale of both dietary supplements and FDA-approved, prescription-only omega 3-based pharmaceutical products.
Unlike most companies in the cannabis- based pharmaceutical space (mainly focused on developing cannabinoids as therapeutics), Potbotics is a biotechnology company that has combined robotics and artificial intelligence to ostensibly streamline cannabis pharmaceutical development. The company is commercializing a product called Brainbot, a physician-facing tool designed to identify the right combination of cannabinoids found in specific marijuana strains to maximize the therapeutic benefits of cannabis for treating patients with concussions, epilepsy, and other neurological indications. “Think of Brainbot as a super EEG medical device that allows healthcare providers to evaluate and quantify in real time a brain’s reaction to specific strains of marijuana,” explained David Goldstein, Potbotics CEO. Goldstein added, “This will allow healthcare providers to analyze and determine the right ratio of cannabinoids [and make strain recommendations to patients] for optimal treatment of certain neurological indications.”
CLINICAL TRIAL CHALLENGES
Cannabis’s classification as a Schedule I drug (i.e., illegal with no current medical value) makes medical cannabis research extremely difficult. Also, while the FDA has signaled a willingness to review new drug applications for cannabis-based therapeutics, the agency has yet to issue definitive guidance for regulatory approval of these products.
“The confusion between federal and state laws is a major factor that is causing hesitancy among regulatory bodies regarding the approval of cannabis-based products,” said Castor. For example, he offered, “Federally, a drug cannot be prescribed unless it has undergone clinical trials, yet many states have passed legislation allowing the use of medical marijuana without clinical trials and without identifying specific indications. This must be resolved to ensure patient safety.” Likewise, Petkanas believes that cannabis’s designation as a Schedule I drug is a serious impediment and one that will need to be resolved to commercialize cannabis- based products. He said, “The legal patchwork for cannabis that has evolved in the U.S. suggests that cannabis- based therapeutics will be available only in certain states (which will restrict patient access) and also make it very costly for companies to underwrite product launches in individual states.”
Unlike other prescription drugs, which are exclusively in the purview of the FDA, cannabis-based therapeutics require input from the U.S. Drug Enforcement Agency (DEA). And, the current political mindset at the DEA is not favorable for the current and future development of cannabis-based products. “THC is the only cannabinoid that has any real psychotropic effects, and, despite the possible therapeutic benefits of other cannabinoids like CBD and CBG, they are Schedule I substances, which makes developing any cannabis-based pharmaceuticals quite challenging,” lamented Castor. Petkanas was more sanguine about cannabis’s designation as a Schedule I substance. He said, “The Controlled Substance Act needs to be repealed, changed, or simply allowed to wither away to ensure that much needed cannabis-based drugs can be brought to market to address unmet medical needs.”
There are also several technical and manufacturing issues that must be addressed before cannabis-based pharmaceuticals can be successfully commercialized. First, substantial investment must be made in production facilities to breed and grow various cannabis strains to obtain appropriate chemical compositions to treat specific therapeutic indications. According to Petkanas, this investment must include research on breeding programs, strain construction, cannabinoid concentrations at different stages of plant growth/harvest times, and yield improvements. “As strange as this may sound, crop failure [not having a redundancy of supply] is a serious issue that all players in the medical cannabis industry must address,” mentioned Petkanas.
Second, plant growth, extraction processes, and manufacturing active cannabis- based therapeutics must be conducted according to current good manufacturing practices (cGMP) and rigorous quality standards. “The whole point of seeking regulatory approval is to demonstrate to patients and healthcare providers that our products have been thoroughly reviewed are well characterized and determined to be safe and effective,” stressed GW Pharma’s Schultz.
Third, the method and route of delivery of cannabis-based pharmaceuticals for individual indications will be vitally important. While smoking cannabis is currently the most obvious method to deliver desired therapeutic effects, it may not be the most effective way to maximize its medicinal benefits. “Every patient is different, and we need to offer them alternate delivery methods to best treat their illnesses,” offered Petkanas. He added, “You cannot lockin on a single delivery technology or form of administration for these products.” Castor agrees. “We are currently studying various routes of administration and investigating the use of controlled- release technology to improve the oral and topical delivery of our products to expand the use of cannabis-based products to new indications.”
Finally, determining the appropriate cannabis-dosing regimen for individual therapeutic indications will be critical. Petkanas offered, “Right now we have extremely limited scientific information regarding cannabis-dosing regimens for individual indications. We have to get this right to instill confidence in patients and physicians that our products work and are safe.”
PROVIDER/INSURANCE EDUCATION IS IMPERATIVE
Both Petkanas and Castor agree that the existing confusion about the legality of cannabis-based products will likely have an effect on insurers and third party payers. “At this point, it is really unclear whether payers are going to place these drugs on formulary and reimburse patients who use them medicinally,” stressed Petkanas. Further, Castor suggested that, like the omega 3 fish oil market, where there are both nutritional supplements and omega 3 fatty acid-based prescription drugs, consumers may have to pay out of pocket for medical marijuana, whereas insurers may cover the cost of FDA-approved cannabis-based therapeutics.
Despite any of these challenges, it is undeniable that there is burgeoning demand for medical marijuana and cannabis-based pharmaceuticals in the U.S. However, while the American public appears to be ready for medical cannabis use, it is currently unclear whether physicians will be inclined to write prescriptions for these products. To that point, patient and healthcare provider education was cited by each person interviewed for this article as the single most important factor for successful U.S. commercialization of cannabis-based therapeutics. “Let’s face it, if physicians don’t understand these drugs and are not convinced that these products are safe and effective, then they certainly are not going to write prescriptions for their patients,” emphasized Petkanas. Both Castor and Petkanas believe that cannabis- based products may garner FDA approval as early as next year.