Mankind has long known about the therapeutic benefits of cannabis, but to me, that is hardly enough to support the incorporation of cannabinoid-based medicines into the health care system.
For thousands of years, people have claimed that smoking cannabis relieves pain. When a belief endures for this length of time based on anecdotal information it deserves a deeper dive. The challenge I signed up for when I took the helm at Tetra Bio-Pharma, was to prove this scientifically with a pharmaceutical pathway that underscores our mission and values.
Cannabinoids may be useful in treating chronic pain, reducing opioid use, and helping relieve pain and suffering where traditional pharmaceuticals or alternative therapies have failed. In that case, they could become a game-changer in how we deal with pain. But I am not alone in wanting proof. For several years now, the uptake of cannabis for medical use has been limited because of the absence of scientific data that conforms to the rigorous standards required by regulators, medical associations, and payers.
I saw the end solution to be simple, the road to getting there, not so much.
I became convinced that the only way that cannabinoid therapeutics would be incorporated into the traditional healthcare system was by following a classic drug development program. Discovering how inhaled cannabis works and learning the pharmacokinetics of how pain-relieving chemicals are delivered to the central nervous system, was key to the research we do at Tetra. Fast forward and we are currently investigating CAUMZ™, a cannabinoid-derived medicine that uses synthetic THC and CBD delivered to patients using an inhaler called the Mighty Medic, a medical device created by Storz & Bickell, a wholly-owned subsidiary of Canopy Growth. The device is currently approved for use in Canada and is under review by the U.S. Food and Drug Administration (FDA) as part of the approval process for CAUMZ™.
CAUMZ™ is being investigated for two indications. Our Phase II/III clinical trial called SERENITY© will study CAUMZ™ as a treatment to improve physical functioning and for modulating cachexia progression in patients with advanced cancer. Cancer cachexia remains an unmet medical need even though an estimated 50-80% of cancer patients suffer from it.
Finding evidence beyond anecdotal reports
Despite the anecdotical reports of patients and physicians claiming that cannabis was helpful to manage the constellation of associated symptoms such as loss of appetite, weight loss, nausea, vomiting, fatigue, and pain as of today, there are only a limited number of studies conducted on the condition, and to assess cannabinoids to manage the symptoms. CAUMZ™ dosage and route of administration increase the bioavailability of the drug, signifying an advantage over other cannabinoids and cannabis extracts.
A further Phase II trial called REBORN© is a head to head study investigating the efficacy of CAUMZ™ versus immediate-release oral opioids to measure pain intensity and the onset of action for breakthrough pain in cancer patients. For individuals suffering from debilitating pain, the faster they can achieve relief the better, so if successful, this research may offer an improved quality of life for these patients and reduce their opioid consumption. We are optimistic that CAUMZ is qualified for several FDA regulatory pathways that would see the time needed to have the drug approved and to market considerably reduced.
Another of Tetra’s cannabinoid-derived drugs undergoing Phase II clinical trial (the ‘Plenitude’ study; NCT04042545) in the United States is QIXLEEF™, an inhaled medicine that is being tested for the treatment of uncontrolled pain in advanced cancer patients. Unlike CAUMZ™ which is based on a synthetic cannabinoid, QIXLEEF™ is a botanical product that uses dried flower buds. A Letter of Advice and Type B meeting with the U.S. Food and Drug Administration (FDA) added important information that will evaluate the drugs’ impact on advanced cancer patients with uncontrolled pain. Based on a successful outcome, Tetra would be able to commercialize the world’s very first dried flower botanical cannabinoid drug product for the treatment of uncontrolled pain in patients with advanced cancer.
Orphan Drug Designation
Tetra has also received FDA Orphan Drug Designation for THC in the treatment of hepatocellular carcinoma. Hepatocellular carcinoma (HCC), also known as primary liver cancer, is the most common form of liver cancer and is responsible for 80 percent of the primary malignant liver tumors in adults. It is the second most frequent cause of cancer-related death globally. Tetra intends to leverage the pharmacokinetic and safety data from the CAUMZ Phase I clinical trial to support its Phase II trial of a modified formulation of CAUMZ, under the name HCC 011.
The phase II trial will investigate the efficacy of HCC011, administered in combination with the first line-therapy sorafenib, to improve control disease in inoperable, advanced hepatocellular carcinoma patients. One of the next steps will be a Type B meeting with the FDA to discuss the HCC011 proposed clinical program and overall premarketing requirements.
Clinical Research and the Impact of COVID19
It would be nearly impossible to talk about our pharmaceutical research without acknowledging the impact of COVID19. This has been an unprecedented time where resilience within the Tetra community has shone a positive light on the physical, emotional, and financial hardship being faced at home and around the world.
The pandemic has caused delays in clinical trials for CAUMZ™ and QIXLEEF but we are hopeful to be able to begin patient recruitment as soon as it is deemed to be safe. Our highly experienced employees offered up their expertise in regulatory affairs and quality assurance to help a local business pivot their manufacturing plant to produce N95 medical-grade masks for frontline workers. Tetra supported the company pro bono with the applications necessary to get a Health Canada license. With a focus on the health and safety of our employees, everyone has been working tirelessly from home offices and in facilities conforming to physical distance guidelines to ensure we advance our work.
With a crisis also comes opportunity. Tetra’s decades-long research in ophthalmics created a further opportunity to study the anti-inflammatory properties of our drug candidate PPP003 for a second indication for Cytokine Release Syndrome (“CRS”) to treat certain symptoms of COVID19.
The drug development program for PPP003 was adjusted to support a Clinical Trial Application (CTA) in Canada and an Investigational New Drug (IND) application in the United States for an intravenous sterile finished drug product. We designed the nonclinical safety program and Phase I clinical trial to support Phase II trials in either CRS or ophthalmic disease patient populations. Under an accelerated timeline, a potential drug for CRS could be ready for conditional approval by Health Canada during the third quarter of 2021.
The Phase I study will enroll approximately 100 healthy volunteers and will be conducted at one clinical site located in Montreal, Quebec. The study will include standard safety assessments, pharmacokinetics, and cardiovascular evaluations. The Phase II study will enroll approximately 200 hospitalized COVID19 infected patients with severe symptoms and requiring oxygen supplementation in the United States and Canada. A Phase II sub-study will explore the molecular mechanisms of the cytokine release syndrome in treated and non-treated patients. This latter sub-study will be performed with Tetra’s US partner Onegevity Health and will aim to monitor select cytokines and biomarkers to predict organ damage.
Legitimacy of cannabinoids
Proving the legitimacy of cannabinoids for inclusion into the healthcare system is closer than ever and will lead to greater access for patients based on unequivocal trust. Those in the biopharmaceutical industry know that drug discovery and development is a long game.
They know the difference between medical cannabis and cannabinoid-derived medicine. While the race is on to commercialize cannabinoid-derived drugs for unmet medical needs I see more than enough reason to exercise care and caution to get the job done, not the least of which is putting patients first.
Then, and only then will the maximum benefit of cannabinoids reach their full potential.
Safety and Efficacy of Inhaled Synthetic THC/CBD for Improving Physical Functioning and for Modulating Cachexia Progression in Patients With Advanced Cancer and Associated Cachexia (SERENITY) – NCT04001010
Inhaled Synthetic Cannabinoids Versus Immediate-release Oral Opioids for the Management of Breakthrough Cancer Pain (REBORN) – NCT03564548
Safety and Efficacy of Inhaled Cannabis For the Uncontrolled Pain Relief in Patients With Advanced Cancer (PLENITUDE) – NCT04042545
Safety and Pharmacokinetics of Smoked Cannabis in Healthy Patients – NCT04314804