Therapix Biosciences Ltd., of Tel Aviv, Israel, said top-line results of a small single-arm, phase IIa study of its combination of dronabinol (delta-9-tetrahydracannabinol) and Cannamide (palmitoylethanolamide), THX-110, showed a positive effect on symptoms of obstructive sleep apnea (OSA), a serious sleep disorder. The company next plans to initiate a phase IIb study of THX-110 for OSA in Europe in 2020, Ascher Shmulewitz, Therapix's chairman and interim CEO, told BioWorld.
If successful, the candidate could provide adults with OSA a new medicinal option for treatment of the condition, which is now managed largely with continuous positive airway pressure machines, surgery, weight management, positional therapy and lifestyle changes, according to the American Academy of Sleep Medicine.
Though a number of drugs have gained regulatory approvals for the treatment of symptoms associated with OSA, no drug has been approved for the direct treatment of OSA itself.
The phase IIa trial, conducted at Israel's Assuta Hashalom Medical Center, was an open-label evaluation in which each of 10 adults with OSA received once-daily treatment with THX-110 for 30 days via capsule. Nine of the 10 participants were evaluable after one dropped out due to dizziness. On the primary endpoint, a measure of sleep quality called the ApneaHypopnea Index (AHI) following treatment, 55% demonstrated significant improvement in AHI values (t-test; AHI mean difference 0.013, p<0.05).
Treatment was given in a dose-titration regimen with a maximum dose of THX-110 consisting of 10 mg of dronabinol and 800 mg of palmitoylethanolamide (PEA).
Therapix shares (NASDAQ:TRPX), depressed relative to highs reached ahead of a year-ago near-acquisition of the company by FSD Pharma Inc., fell further on Nov. 7 after Therapix announced a mutual decision to discontinue its proposed merger with Destiny Biosciences Global Corp. But with good news about the OSA program, more than 21 times the average volume of shares traded hands, sending the company's share value up 19.4% on Wednesday to $1.72 at the close.
In THX-110, Therapix has combined a low dose of dronabinol already FDA-approved to treat nausea and vomiting caused by chemotherapy with Cannamide, its oral formulation of PEA, a cannabimimetic compound and lipid messenger. In July, Health Canada's Natural and Non-prescription Health Products Directorate granted Cannamide a license for use as an anti-inflammatory and to help relieve chronic pain.
Cannamide, an endogenous fatty acid amide that belongs to the class of nuclear factor agonists, is hypothesized to enhance the activity of cannabinoids by potentiating their affinity for their receptor and by inhibiting the metabolic degradation of endocannabinoids, leading to enhanced duration of effect.
The real opportunity that combining Cannamide with dronabinol presents is to reduce the dose of cannabis to deliver more benefits with fewer side effects, Shmulewitz said. Higher doses of dronabinol increase the risk of psychoactive effects, including psychosis.
Based on the work of Shmulewitz's long-time partner, Raphael Mechoulam, dronabinol and Cannamide are thought to induce a reaction they called the "entourage effect," a synergistic effect in which cannabinoids work together in a mechanism similar to the body's own cannabinoid system. Mechoulam, a professor emeritus at Hebrew University of Jerusalem, is a scientific advisor to Therapix.
Therapix exclusively licensed the IP behind Cannamide from Dekel Pharmaceuticals Ltd., an Israeli private company controlled by Shmulewitz, in May 2015.
Shmulewitz, a physician-scientist, said that as Therapix advances THX-110, it is looking at different opportunities to advance the program, such as substituting a botanically sourced cannabinoid for dronabinol because of the changing regulatory environment outside the U.S. The phase IIb study in OSA is likely to use a botanical cannabinoid, he said.
In addition to OSA, THX-110 is also being evaluated for symptoms related to Tourette syndrome, an indication for which the company is seeking an FDA orphan drug designation.