Ethicann and Ilera Forms Partnership to Develop and Manufacture of Botanical THC to Treat Chemotherapy-Induced Nausea and Vomiting

Cannabis, a flowering plant as a potential source for an approved treatment to treat Chemotherapeutic- Induced Nausea and Vomiting (CINV)
Cannabis, a flowering plant as a potential source for an approved treatment to treat Chemotherapeutic- Induced Nausea and Vomiting (CINV)

Canada-based Ethicann Pharmaceuticals and Ilera Therapeutics announced a development and commercial supply partnership for a highly purified botanical THC-based product for the treatment of chemotherapy-induced nausea and vomiting (CINV).

Among the adverse effects of cancer, nausea and emesis (vomiting and/or retching), are generally the most feared by the patients.

While these side effects can also be cause by surgery or radiation therapy as part of anti-cancer treatment, chemotherapy-induced nausea and vomiting (CINV) is generally considered the most severe and distressing.

Chemotherapy-induced nausea and vomiting

When a patient is treated with chemotherapy, sensors in the digestive system and brain detect its presence as a foreign substance. In a complex series of signals among the brain and the mouth, stomach, small intestine and bloodstream, the medication stimulates the “vomiting center,” the area postrema, a structure in the medulla oblongata in the brainstem that controls vomiting.

Several neurotransmitters are implicated in the control of nausea and vomiting include acetylcholine, dopamine, histamine (H-1 receptor), substance P (NK-1 receptor), and serotonin (5-HT3 receptor). When, as a response to chemotherapy, serotonin and substance P, are released, a nausea and vomiting reflex is triggered. This is the body’s effort to get rid of the foreign ‘chemotherapeutic’ substance.

Onset of CINV

Some people experience CINV within the first few hours of receiving chemotherapy. This is often referred to as acute emesis or acute nausea and vomiting and commonly begins within one to two hours of chemotherapy and usually peaks in four to six hours.

Other patients don’t feel symptoms the day of chemotherapy but may not immediately develop nausea and vomiting. However, CINV may also occur more than 24 hours after chemotherapy, or, in some cases, within next few days. This condition is called delayed emesis or delayed nausea and vomiting.

A separate form of CINV called anticipatory emesis may occur prior to treatment with a new cycle of chemotherapy as a conditioned response to stimuli such as the smells, sights, and sounds of the treatment room in patients who have developed significant nausea and vomiting during previous cycles of chemotherapy.

CINV occurs in approximately 80% of the new 23.6 million cases of cancer annually worldwide. And while much progress has been made in the development of novel treatment options, it remains an important adverse effect of cancer treatment – and represents a major unmet medical need.

Prescription drugs

A number of prescription pharmaceutical agents are used as anti-emetic therapies to prevent or minimize CINV. Dexamethasone, a synthetic adrenocortical steroid, used to treat inflammatory conditions, is most commonly prescribed. This drug is also very effective in treating CINV. In some cases, serotonin receptor agonists called 5-HT3 have been effective when used in combination with dexamethasone.

But not all agents alleviate the debilitating symptoms of CINV. Some patients report that these agents make them feel drugged, lethargic, and even delusional. As a results, research into effective treatment options is ongoing.

Cannabis-based ethical drugs

One treatment option includes cannabinoids. Cannabinoids have shown reasonable success in treating the symptoms of CINV. Two medicines, nabilone, an orally available cannabinoid agonist marketed as Cesamet™ (Valeant Pharmaceuticals), and dronabinol (Marinol®; Unimed Pharmaceuticals and Syndros®; Insys Therapeutics ), an orally-administered synthetic form of delta-9-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis, have had some success. These agents are available in oral and inhaled solutions, and both have been approved for treatment of CINV.

Since the FDA-approval of these agents in 1985, nearly 30 clinical trials have been conducted that show that synthetic cannabinoids are superior to traditional dopamine receptor antagonist medications for the treatment of CINV. And the The American Society for Clinical Oncology (ASCO) antiemetic guidelines updated in 2017 recommends that the FDA-approved cannabinoids, dronabinol or nabilone, be used to treat CINV that is resistant to standard antiemetic therapies. [1]

However, according to the National Cancer Institute only a limited number of human clinical trials have studied the effect of natural cannabis for treatment of CINV.

While focusing on CINV, natural cannabis can also be used for other types of nausea. Most medical evidence pointing to a therapeutic benefit have come from strains containing some degree of THC. And the therapeutic outcomes largely depend on the concentration of THC.

Ethicann, founded in 2018, has extensive experience in the Canadian and U.S. pharmaceutical and Canadian cannabis industries.  The company’s strict focus is the commercialization of cannabis-based ethical drugs that will be submitted for marketing approvals to Health Canada, the U.S. Food and Drug Administration (FDA) and other global pharma regulatory authorities.

Ethicann completed its initial financing earlier this year and recently held a successful Pre-IND meeting with the US Food and Drug Administration (FDA) to discuss the 505(b)(2) requirements for a marketing approval for CAN-001, its first commercial product designed to treat chemotherapy-induced nausea and vomiting (CINV).

Ethicann has also recently initiated discussions with Health Canada on the regulatory pathway for its second pharmaceutical product and contemplates requesting a Pre-NDS (New Drug Submission) meeting later in 2019.

Licensed growers and extractors

After the initial meeting with representatives of the FDA, Ethicann finalized its development and manufacturing agreements with the licensed cannabis producer/extractor Ilera Therapeutics, part of the Ilera group of companies, to provide investigational pharmaceutical drugs.

In their partnership, the two companies share a keen interest in the development and commercialization of cannabis-based pharmaceuticals that target important disease areas and that will be subject to the rigors of global drug regulatory review.

As part of the agreement, Ilera Therapeutics will develop and manufacture a highly purified botanical THC-based product that can be used by Ethicann to conduct a limited clinical study to support a market approval application that Ethicann will file initially in the United States for its CAN-001 product.  Ethicann will then seek approvals in other global markets, using the same clinical data.

The global market for treating CINV with THC is estimated at USD $2.66 billion.

Reference

[1] Hesketh PJ, Kris MG, Basch E, et al.: Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 35 (28): 3240-3261, 2017. [