LONDON—Aimed at developing and commercializing cannabis for treating cancer, while breaking down barriers blocking medical marijuana use, London-based GW Pharmaceuticals has commenced a Phase Ib/IIa clinical trial for the treatment of recurrent glioblastoma multiforme (GBM).
GBM is a particularly aggressive brain tumor that forms from abnormal growth of glial tissue. According to the New England Journal of Medicine, GBM accounts for approximately half of the 22,500 new cases of brain cancer diagnosed in the United States each year. Treatment options are limited and expected survival is a little over one year. GBM is considered a rare or orphan disease by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Biopharmaceutical GW has established a leading position in the development of plant-derived cannabinoid therapeutics and has a deep pipeline of additional clinical-stage cannabinoid product candidates targeting not only glioma, but also epilepsy (including an orphan pediatric epilepsy program), type 2 diabetes, ulcerative colitis and schizophrenia.
GW’s study, launched Nov. 11, is a 26-patient, multicenter, two-part study with an open-label phase to assess safety and tolerability of GW cannabinoids in combination with temozolomide, and a double-blind, randomized, placebo-controlled phase with patients randomized to active or placebo, and with a primary outcome measure of a six-month progression-free survival.
“We are very excited about moving this compound into further human study and the prospects of cannabinoids as new anti-cancer treatments. This is GW’s first clinical study of cannabinoids as a potential treatment to inhibit tumor growth,” Dr. Stephen Wright, director of research and development at GW, stated in a news release. “We believe this clinical program demonstrates the flexibility and broad application of GW’s cannabinoid platform to treat significant, unmet therapeutic needs.”
Mark Rogerson, spokesperson for GW Pharmaceuticals, tells DDNews that GW’s “extensive research into the pharmacology of cannabinoids continues to yield highly promising data and new intellectual property across a range of therapeutic areas. GW continues to invest in research to accelerate further growth and value creation through the development and licensing of several new cannabinoid drug candidates.”
Despite the medicinal and recreational use of cannabis for centuries, the identity of its main psychotropic constituent remained unknown until 1964 when Raphael Mechoulam, Yechiel Gaoni and Habib Edery from the Weizmann Institute of Science in Rehovot, Israel, isolated and synthesised tetrahydrocannabinol (THC).
It was subsequently established that this compound is responsible for the psychotropic effects of the plant, one early hypothesis being that since THC is so hydrophobic it induces these effects by interacting with cell membrane lipids. However, as more was learned about the pharmacology of THC and of synthetic cannabinoids such as CP55940 that induce THC-like effects, it became increasingly likely that these effects must be mediated by a distinct family of receptors.
“Our objective is to utilize cannabinoid therapy, in combination with the standard of care therapy temozolomide, to inhibit tumor growth and prolong survival,” Rogerson said. “If the results from this current Phase Ib/IIa safety/tolerability trial are positive, GW expects to move the compound into the next stage of clinical evaluation which would be a Phase IIb dose-ranging study.
“The study objective is to assess the tolerability, safety and pharmacodynamics of a mixture of two principal cannabinoids, THC and CBD in a 1:1 allocation ratio, in combination with temozolomide in patients with recurrent GBM,” he said.
“Secondary endpoints include additional pharmacokinetic and biomarker analyses and additional measurable outcomes of tumor response,” Rogerson said. “We hope to be able to identify meaningful signals of a positive response to treatment with cannabinoids in these patients.”
Not only has GW Pharmaceuticals developed a proprietary and validated cannabinoid technology platform, but it has formed constructive collaborations with leading international scientists, universities and institutions in the field, he said. In addition to this expanding research network, GW also supports clinicians who approach the company to explore the potential of cannabinoids in the clinic through investigator-initiated studies.
GW is the first company to market a natural cannabis plant derivative under regulatory approval, with its lead product, Sativex, approved now in 22 countries and on the market in several of these. The United States is not on the list and lags behind in cannabis research.
Wai Liu, an oncologist at the University of London’s St. George’s Medical School and author of another cannabis study, told U.S. News that “quite a lot of cancers should respond quite nicely to these cannabis agents. If you talk about a drug company that spent billions of pounds trying to develop these new drugs that target these pathways, cannabis does exactly the same thing—or certain elements of cannabis compounds do exactly the same thing—so you have something that is naturally produced which impacts the same pathways that these fantastic drugs that cost billions also work on.”
Liu stresses that his research focused on chemicals that would not intoxicate patients.
As for the United States, the cannabinoids dronabinol and nabilone are approved by the FDA for combating the side-effects of chemotherapy, but no cannabinoids are currently approved for treating cancer itself.
Kris Hermes, a spokesman for the pro-medical marijuana group Americans for Safe Access, says that American scientists looking into cannabinoids “have often given up in disgust” because of “the harsh climate for research” in the United States.
Researchers must first receive approval from the National Institute on Drug Abuse (NIDA) and also from the U.S. Public Health Service before looking into the plant’s possible benefits. NIDA holds a monopoly on cannabis used for research and requires all scientists to use plants grown at the University of Mississippi.
According to Liu, European countries are the primary drivers of cannabis research. At the same time, he believes business interests may have historically played a role in deterring research into marijuana-derived substances.
