Dr Mark Ware, Chief Medical Officer at Canopy Growth Corporation

Mark Ware, Chief Medical Officer at Canopy Growth Corporation, shares his vision for the future of the medical cannabis sector and says there is massive patient demand; however, research and clinical trials have yet to catch up to position cannabis as a respected medical product.

Could you please start by introducing yourself to our international readers?

I am Canopy Growth Corporation’s Chief Medical Officer with overall responsibility for the advancement of research and Spectrum Therapeutics, Canopy Growth’s global medical cannabis brand. I am also an Associate Professor at McGill University sitting as the Director of Clinical Research of the Alan Edwards Pain Management Unit at the McGill University Health Centre, as well as an executive director of the non-profit Canadian Consortium for the Investigation of Cannabinoids. Previously, I served as Vice Chair of the Federal Task Force on the 2016 Legalization and Regulation of Cannabis in Canada, which was a body assembled specifically to advise the Canadian authorities on its medical and non-medical strategies for the sector.

What role is Canopy Growth Corporation playing in the ongoing “pharmatization” of the medical cannabis industry?

You have to go back to the Canadian context and how we were established at a juncture at which nationwide regulations allowed for companies to apply for licences to grow and produce cannabis for medicinal purposes. There were a number of smaller companies that amalgamated to comprise Canopy Growth Corporation and its subsidiary  – now known as Spectrum Therapeutics – which is essentially the brand within that is focused on the medicinal and therapeutic aspects.

Spectrum has become a multinational effort to run trials across all areas of the globe where we are operational with a view to providing evidence-based data around safety and efficacy for different forms of cannabis when applied to treating different medical conditions. As such, we are assuming a highly proactive role in the professionalisation of the cannabis industry as the sector more traditionally associated with the vice industry starts to take on pharmaceutical grade characteristics.

Canopy has matured into one of the most credible companies in the medical cannabis space. Not only are we tremendously well resourced and understand the true scientific potential of cannabis-derived therapies, but we are steadfast into our commitment to furthering the understanding of cannabis as a medicine.

How easy are you finding it to gather the clinical data and real world evidence to validate the efficacy of cannabis-based therapies?

We have to recognise the stark fact that millions of consumers are already utilising cannabis-based products as a form of self-medication for anxiety, insomnia or pain, so there is already a wealth of anecdotal evidence out there, but the responsibility is on industry actors like Canopy to fill in the gaps and provide more systematic data sets. Patients all around the world perceive the beneficial impact of cannabis-based therapies and are clamouring for greater study into this area of medicinal science. We, at Canopy, have listened hard and are trying to produce the requisite data to systematically support the alleviation of symptoms that they have been describing.

It’s important to consider that the manner in which the medical cannabis space has evolved has been rather distinctive. Much of the original impetus has come from grassroots-up rather than from being imposed top-down. There are dual forces at play. On the one hand, there is massive patient demand for unmet needs for conditions like pain and insomnia, which are placing huge burdens on society in terms of lost productivity. Patients are actively calling for better access to cannabis-based treatments so that they can better manage their symptoms. On the other hand, a solid body of science is emerging that understands how the compounds and components interact with our bodies through a unique system of receptors. In other words, we are acquiring an ever better understanding of the pharmacological effects that explain why patients might feel how they do.

The gap in between these two aspects is the clinical trial evidence. When compared to standard drug development, the cannabis industry is entering the process back-to-front. We already have the drug as well as countless patients who are reporting an alleviation of their symptoms. What we still need to accomplish, however, is to backfill the data to understand an optimum therapeutic use in a classic medical context.

Given that the main bottleneck seems to be a need for much greater levels of clinical research. What is the prospect of cannabis firms cooperating with the conventional pharma industry to fill in these gaps?

We’ve already seen a few limited signs of this such as Tilray’s partnership with Novartis’ subsidiary Sandoz, and I would expect to see a lot more of these types of interactions to materialise as time progresses. Right now, those cannabis players that are serious about creating pharma-grade therapies are shouldering the risk of early clinical research, but I would be astonished if the big pharma companies are not watching the data very carefully with a view to stepping into the fray once some phase III ready assets come on stream. There will be political and social reasons behind why they are not yet ready to engage, but it can only be a question of time before this starts to happen.

Companies like Canopy Growth just need to keep our heads down and carry on forging ahead with pharmaceutical style rigor because we strive to ultimately put these therapies in the physician’s toolbox and therefore need a quality and style of product that the practitioners are going to be familiar with and comfortable in prescribing. Similar to traditional biotech, Spectrum Therapeutics, is operating as a specialty pharma type play, aiming to take away much of the risk associated with early stage clinical testing. Once we get close to that, the big traditional drug makers are certain to want to get involved because this is going to be a very disruptive influence on their classic business model, and they will end up losing out if they don’t themselves join the game.

How can you be so confident of its medical cannabis’ capacity to disrupt the conventional medical space?

Well, for example, cannabis presents an excellent solution to the opioid crisis that is currently ravaging North America given that it constitutes a much more natural based remedy without the same addiction profile. There is already powerful evidence from large-scale epidemiological studies that patients have been deploying cannabis-based therapies to reduce their opioid intake and an equally strong scientific rationale around how activation of cannabinoid receptors stimulates the release of opioid peptides.

In short, using a combination of the two together can be considerably more effective than when deployed in isolation. So the concept of a cannabinoid-opioid synergy is underpinned by solid scientific understanding, but the problem is we are yet to have sufficient data from clinical trials to determine how much of each to take so as to elicit optimum effect. Nor do we yet have the requisite trial data to know how quickly to safely reduce the opioid dosage. These lines of enquiry are still waiting to be properly explored. Once it happens, though, the way that we manage pain will clearly need to be thoroughly rethought, and we will have a tool at our disposal with which to reverse the opioid epidemic.

To what extent is the prevailing clinical trials process fit-for-purpose when it comes to evaluating the efficacy and safety profile of cannabis-based therapies?

Frankly cannabis doesn’t always fit the classic pharma clinical trials model very well.  Because cannabis-based medicine is plant derived, we’re talking about therapies that contain multiple compounds unlike most pharmaceuticals, which tend to contain unique single agent tightly controlled substances. Plant derived medicine comes from natural components, not chemically synthesised substances, so there is an inherent, natural variability that doesn’t necessarily align well with the rigors of the clinical trial 4-phase sequence.

Nonetheless, there are two main evidence pathways that we must pursue. One is, of course, navigating the clinical trials, which constitute the gold standard in determining whether a proposed treatment has direct effects on the outcome of interest above and beyond placebo, so it constitutes a powerful methodology to determine causality of response. The other is ‘real world evidence’ (RWE) as a driver of safety signals because when you have thousands people using a product these indicators simply don’t tend to show up in smaller clinical phase III clinical trials. Many conventional drugs look like they’re safe and effective, and it is only with real world evidence that some of the main safety signals are picked up. With medical cannabis, we have an opportunity to be capturing that information from real world use at the same time as conducting phase I and phase II research to establish efficacy. It's a unique opportunity to play with two kinds of research simultaneously.

Ultimately, it will be up to regulators to look at the files we submit and the data packages we put together from both clinical trial programmes and RWE and come to decisions about whether these drugs are acceptable for market authorisations, medical use, and even reimbursement.

Please tell us more about your current clinical research pipeline.

Our clinical research programme is heavily driven by patient experience and tends to be built around triad of pain management and mood disorders of anxiety and insomnia. Many of these trials are ongoing, and some are at the planning phase and awaiting regulatory approvals. During the course of our research we have noticed that cannabis tends to be more effective for chronic pain than acute pain, which exhibits a different phenotype, so we have been scoping in on that area and are targeting smaller sub-populations. Cannabinoids are neurologically active so naturally our approaches tend to be very CNS pathway focused, but there are other smaller therapeutic areas that are registering positive signals as well. 

What would you say most differentiates you from your competitors? 

Our key differentiator is our relentless focus on research and not just supporting small isolated studies, but large-scale, coordinated focused programmes with three to five year deliverables. Not many of our competitors can lay claim to such a prolonged commitment and long-term strategy. The Spectrum Therapeutics brand stands for stringent clinical research, robust science and approved medicine. We strive to be seen as a credible research partner and to be a key protagonist in elevating cannabis to the level of a true medicine that clinicians are keen to prescribe.

How are you going about winning over the hearts and minds of practitioners and patients so that they are comfortable prescribing and consuming medical cannabis?

We still have a lot of work to do on this front in jurisdictions all across Europe because this is a drug that comes with a certain level of baggage arising from 70 years or so of prohibition. We have to work proactively to dispel the stigma and encourage all stakeholders – form patients and doctors to regulators and payers – to take this therapeutic mechanism seriously again and to conceptualise cannabis not as a drug of abuse or gateway narcotic, but a drug of immense medical value. It is imperative to reclaim the image, because let’s not forget that medical cannabis is making a comeback: plant-based medicine has a very long and rich history that actually precedes chemically synthesised therapies.

The way to accomplish this is to generate sound data and to disseminate that information to those stakeholders who need it. The data generation comes from extensive clinical research, scientific experiments and real world evidence of observing people using cannabis so that we can understand what the safety signals might be, define the indications and determine the optimum dosage and delivery mechanisms. This, in turn, means we can provide a solid evidence base over the years that can inform good quality clinical decision-making and can be presented to clinicians in a format that they are familiar and can readily identify with.

Another aspect that perhaps distinguishes Canopy Growth from many of its competitors is our commitment to education and helping clinicians of different stripes – whether that be the pharmacists, specialists physicians or nurses. We see it as our task to help them navigate what medical cannabis is all about and have been putting together world-class seminars and training programs because this is not yet a subject that is covered well in many medical schools.

How would you describe Canopy Growth’s European expansion strategy?

We notice there are plenty of different approaches in play as integrated cannabis MNCs scramble to get a piece of the action in Europe, which has only just started to open for business. Our two main efforts centre upon Germany and the UK where we have operating companies already licensed to move products and supply patients. We are also active in Czech Republic and Poland too and maintain a facility in Denmark that is cultivating to GMP standard. The overarching strategy is essentially to have European operations based out of Germany and Britain that can facilitate distribution into other markets throughout the region as and when they open up and become legal.

Europe is tremendously exciting for us because of the market size. We’ve learned from the Canadian context that a figure of 1% is appropriate when estimating market size, which translates to 7.5 million consumers for the 750 million strong regional population. Moreover, our five-year experience in a regulated market in Canada has given us a lot of experience as to what works and what doesn’t and has set us up well to make the most of the emerging opportunities.

How has this been reflected in your M&A activity?

Recently we acquired the “Cannabinoid Compound Company (C³),” a leading German manufacturer and distributor of dronabinol, a pure chemical compound with standardised concentrations of tetrahydrocannabinol (THC), which is already on the market for nausea and palliative cancer care in Denmark, Germany, Switzerland and Austria. This not only presents Spectrum Therapeutics, with an expanded envelope of medically validated suite of cannabinoid therapies, but an entire infrastructure of production, distribution as well as sales and marketing capabilities. Crucially this includes decades of understanding about the dynamics of the local landscape, the realities on the ground and how to tap into pharmacy and medical specialists' networks. It’s really been about bringing all the different pieces of the jigsaw together from our production expertise to their infrastructure and placing it all under a solid, cohesive and streamlined management.

Meanwhile, we have taken majority stake in BioSteel Sports Nutrition that diversifies our offering and confers a significant platform with which to enter the sports nutrition and hydration segment, while simultaneously laying the groundwork for deepening our cannabidiol (CBD) offering. This is a very interesting molecule that is already being used in many formats in Europe and North America predominantly in an unregulated manner, but which could have significant therapeutic potential. The use and acceptance of CBD-based products in the professional sports landscape is already radically shifting. We have witnessed the negative effects of prescription painkillers, and athletes are on the lookout for healthier alternatives with considerable interest in a more standardised, high quality, controlled and reliable product.