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Can marijuana be made into a tried-and-true prescription medication, one that could be covered by health insurance? According to results from a recent study published in The New England Journal of Medicine, yes, it most certainly can.
The study involved a drug called Epidiolex, formulated by the British company GW Pharmaceuticals. Epidiolex’s main ingredient is cannabidiol, or CBD — a component of marijuana with medicinal properties that doesn’t get anyone high.
The recently published study assessed whether Epidiolex could effectively — and safely — treat children with an epileptic disorder called Dravet syndrome, a condition marked by frequent and life-threatening seizures that are difficult to treat with conventional drugs. There are currently no approved medications for Dravet syndrome in the US, and if Epidiolex is approved by the FDA, it would become the first drug specifically designed to treat this neurological disorder.
Justin Gover is the CEO of GW Pharmaceuticals, and he’s been with the company practically since its inception 18 years ago. Prior to running GW, Gover worked on the business development ends for other pharmaceutical companies, but the promise of new therapies derived from phytocannabinoids — cannabinoid compounds found only in plants like Cannabis sativa — drew him toward exploring the possibility of making pharmaceuticals from weed.
Epidiolex is not GW Pharmaceuticals’ first foray into medicines made from marijuana. In 2010, the United Kingdom approved Sativex, a spray made with THC and CBD, which is currently used to control spasticity in patients with multiple sclerosis. Over the past seven years, Sativex has been approved in nearly three dozen countries, although it has not been approved for medical use in the US, likely due to cannabis being illegal on the federal level, meaning the product is not eligible for FDA testing or regulation.
As a result, GW has focused its efforts on Epidiolex for American markets, and to date, the drug has proven successful in human clinical trials with astounding results. Unlike other cannabinoid-based pharmaceuticals (e.g. Marinol), Epidiolex is made directly from cannabis plant extract, not from synthetic chemicals cooked in a lab. And unlike other heavy drugs used to treat seizures, such as anticonvulsants and tranquilizers, the side effects from Epidiolex are relatively minimal — making it ideal for child patients.
Just a few weeks ago, Epidiolex passed phase III clinical trials, meaning it’s been shown safe and effective for treating a particular health condition in humans. It will likely take another year before the FDA and DEA finalize approvals and scheduling for Epidiolex, but the markets appear optimistic: GW is currently valued over $3 billion, and could reach its first billion dollars in sales within the next couple of years. We caught up with the CEO to discuss the groundbreaking work of the pharmaceutical company.
MERRY JANE: You’ve worked for pharmaceutical companies for most of your career. How did you end up at GW Pharmaceuticals, a company specializing in drugs made from cannabis?
Justin Gover: As we’re all aware, there’s a long history of medicinal use of cannabis in the literature. When I first joined GW Pharmaceuticals 18 years ago, there was very little modern science in that area. The reason I got involved — for me, and for Dr. Geoffrey Guy, our chairman and founder — was a realization that there was an opportunity to evaluate, in a truly scientific way, a plant that had become very controversial for reasons associated with its recreational use, as opposed to looking in a serious, scientific way, at the medicinal properties of molecules in the plant.
What advantages do phytocannabinoids have over conventional pharmaceuticals for treating seizure disorders?
I think, as of 18 years ago, we didn’t know. We didn’t know if phytocannabinoids were special. We didn’t know whether they could be better or worse, or even meet the standards of medications. My mission, and my company’s mission, is to apply the rigors of modern science and the rigors of pharmaceutical development to demonstrate whether a certain phytocannabinoid or a mixture of phytocannabinoids has true scientific value, whether they are safe and efficacious, whether they can be manufactured in a reproducible form, and then made available through the FDA process. Our views of this come from the scientific view that a lot of these molecules could become very important and could add value to existing therapies. But it’s still our job to prove that.
Epidiolex, a CBD formulation, may not have been successful in our trials, though fortunately it was. In the case that it failed, we would’ve learned an unfortunate lesson, but we would have realized that we had to think about another application for the cannabinoid. We do think phytocannabinoids, in general, have potential applicability across a range of areas. We believe we’ve shown the efficacy of CBD in extreme forms of epilepsy. We have some promising proof-of-concept data for CBD in a study on schizophrenia. We developed Sativex as a prescription medicine in Europe for patients with multiple sclerosis.
The development of a pharmaceutical product tends to cost in the billions of dollars. When you’re testing and developing a potential prescription drug, you have to prove each step along the way. It’s not just, “Does it work?” We have to show, “What’s its safety profile on its own? What’s its safety profile when other drugs are taken at the same time? What’s its profile when it’s taken with food?” It’s that kind of information that we have to show to the satisfaction of the FDA in order to make a medicine like Epidiolex available.
What is it about the most recent study in The New England Journal of Medicine that’s different from other CBD studies, such as those that have come from Dr. Raphael Mechoulam’s lab at the University of Tel Aviv?
This is the first randomized, placebo-controlled clinical trial. This is a study that’s been designed with input from epilepsy experts, approved by the FDA, conducted by epilepsy specialists across the United States and abroad, to compare a pharmaceutical CBD formulation — not a number of distinct oils, but a specific, pure CBD product — against a placebo in a double-blind fashion. “Double-blind” means that neither the patient nor the physician, nor the parent company, knows what the patient is taking during the study. It’s only at the end of the study where you “unblind” — or reveal — which patients have been on either the active drug or the placebo to understand how the drug works. You have to be able to demonstrate that the active compound is statistically superior to the placebo. That is the gold standard for clinical trials, and I think it justified being published in The New England Journal of Medicine, because this was really the first true high-quality, clinical control trial that had demonstrated the highest standards of modern science for the activity of CBD in a seizure disorder.
Epidiolex’s main ingredient is CBD, but GW’s website says it contains other cannabinoids as well. Can you tell us what those other cannabinoids are, and are they active?
In terms of its composition, it’s plant-derived, but the formulation is essentially pure cannabindiol. There are trace quantities of some other cannabinoids in the formulation, but they are not active. The product is essentially 99 percent CBD with trace quantities of other cannabinoid and non-cannabinoid components. Epidiolex is designed to be as pure as one is able to make from a plant process. We have created not just an extraction process, but a crystallization process that pulls out the CBD from an extract, then we clean it up.
Did you experience any special regulatory obstacles to receive approval for the study from the FDA?
Certainly. There are two levels of complexity. The first is — and this applies to any investigational medicine — in order to do a clinical trial of this kind, you need permission from the FDA. You need what’s called an “investigational new drug” or IND, which says the product has met criteria for safety in order to be exposed to humans. We do a lot of toxicology, pre-clinical work, and animal toxicology regarding safety. The protocols of the clinical trial design have to be submitted to the FDA to ensure they have scientific rigor. Those protocols are also approved by all the hospital sites, by their institutional review boards. Those are common to all pharmaceutical clinical trials.
Because Epidiolex is a cannabinoid, the additional layer of complexity is that it’s a Schedule I substance. In addition to all of the FDA approvals I’m referred to, our trials require that each hospital site that is storing product — which of course they all have to do — is inspected and licensed by the DEA. The DEA will issue those sites with a Schedule I license that allows the hospital to store the product in a secure location and dispense it to patients.
What happens with scheduling once Epidiolex receives approval from the FDA?
In the event of Epidiolex getting approved by the FDA as a prescription medicine, there are a set of automatic changes. The definition of a Schedule I substance in the United States under the Controlled Substances Act means something has no accepted medical use. If Epidiolex gets approved by the FDA, then it has medical use. At that point, Epidiolex will get put into a different schedule by the DEA and then made available by prescription.
What do you anticipate will be Epidiolex’s new scheduling, if approved?
It is the decision of the FDA and the DEA. We are aspiring for the product to be scheduled at Schedule IV, which would be where most anti-epileptic drugs are.
This is not rescheduling of marijuana. This is not rescheduling of CBD oils in general. It’s rescheduling of a product approved by the FDA which doctors can write a prescription for and that health insurance would cover. The distinction, for us, is very, very important. You can’t extrapolate from our study and then apply it to anything else connected to CBD or other phytocannabinoids.
For instance, in the study published for children with Dravet syndrome, that would lead — if approved by the FDA — to the approved use of Epidiolex in the treatment of Dravet syndrome. It doesn’t mean it’s been proven that it’s good for everything and everyone. It means it’s only been approved for use in patients with that diagnosis.
When will Epidiolex hit the US market?
The plan is that we’re finalizing a regulatory submission package to the FDA. That submission is queued to be filed with the FDA in the coming months. The FDA will review that, and the review timeline is likely to be between seven and ten months. And then the DEA has to reschedule, and that’s up to a three-month process. If you take all those steps together, assuming everything goes well, it would be approved and available next year.
CBD has a lot of promise for treating other conditions besides epilepsy. Does GW have plans to study Epidiolex for other conditions?
First and foremost, we’re continuing to study CBD in other types of epilepsy. In addition to the study published a few weeks ago, we’ve already conveyed that we have positive results for another form of epilepsy called Lennox-Gastaut syndrome. We’re doing another study in a highly resistant seizure disorder called tuberous complex. We’re also conducting another study for a condition related to this called infantile spasms, spasms occurring in young infants less than a year old that are very difficult to treat. And we continue to evaluate CBD in other diagnoses of that kind as well.
In addition to that, we’re interested primarily in looking at other phytocannabinoids. We have significant research efforts now into a cannabinoid called CBDv, which occurs in the natural plant. We’ve developed a manufacturing process to develop a specific formulation for treating children with autism, and we’re looking at CBDv for other conditions within the autistic spectrum.
We’re also looking at a combination of THC and CBD in patients with a very aggressive form of brain cancer. And the list goes on. I think you’ll continue to see from GW further, high-quality products of different cannabinoids and different combinations of cannabinoids for treating diseases.
Does GW Pharma have an official stance on marijuana legalization?
We make no apologies for it: We’re a commercial organization. We develop medication for patients who have significant, unmet needs. We’re not a political organization. As such, we don’t have a set of positions whether it’s medical marijuana or not.
Our position is fairly simple regarding our view of cannabinoids — so we’re clear about one thing — we do believe there’s a reason the FDA exists. There’s a reason why doctors rely on prescription medications in order to treat complex conditions. We think it’s important that cannabinoids are held to the same standards as other types of medications that physicians could prescribe. Particularly, if you take some of the children we’re treating with Epidiolex, these are children with very complex conditions that are taking multiple other medications. It’s hugely important that — there’s a responsibility on us and on society — that we understand the impact of putting a new molecule into a patient like that.
We’re very excited at GW for the potential for cannabinoids, but we’re also very passionate about the view that this should be done with real science, with the outcome being FDA-approved prescription medications that have been appropriately tested and manufactured for patient safety. Patients deserve the right for a prescription option that has been approved by the FDA and meets the requirements for modern prescription medication.
If we do this the right way, we can end up with an outcome that shows cannabinoids have critical roles to play in modern medicine, but they must be held to the same standards that other medications have also met. Just because it’s a cannabinoid does not mean we should ignore the development process. We believe one should adhere to it.
What should readers ultimately take from these latest developments for Epidiolex?
Let’s take a moment here to reflect on just how exciting these results really are from The New England Journal of Medicine study. What’s most important is that we have created a medication that’s been shown, in a clinical trial conducted at the highest possible standards, that it can reduce the seizure burden in one of the most difficult types of epilepsy to treat. It’s a great outcome for science. It’s a great outcome for the potential for these kinds of medications. It’s exactly what the physician community has been wanting to see. Above all else, I think it’s important to consider what we’re doing and center this back on the patient.
We really are doing this because we want to help patients who are suffering from very complex neurological conditions to find new treatment options. There’s no better outcome for us than to see and hear stories of children in our studies who have dramatic improvements in seizure control and in their lives. That really is what drives our company to do what we do.
For more information on GW Pharma, visit the company's website here.
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