GW Pharmaceuticals’ (LON:GWP) Sativex (nabiximols) for advanced cancer pain is likely to have strong US market uptake upon expected FDA approval, physicians said. The drug will likely be a Schedule II or III controlled substance, although there is debate on the abuse potential, they added.
The US market is receptive to nonopioids that can alleviate cancer pain, considering that maximum pain mitigation with opioid treatment is common, the physicians noted. When it comes to abuse, while there have been no cases of Sativex abuse where it is approved, its expected scheduling based on its cannabis origin has elicited mixed opinion.
Sativex is a spray formulation of two active ingredients, tetrahydrocannabinol (THC) and cannabidiol (CBD), both of which are cannabinoids. It is intended for patients who have inadequate analgesia with optimized chronic opioid therapy.
The drug is expected to garner positive Phase III results and subsequent FDA approval, this news service reported 10 July.
Sativex will be a well-adopted adjuvant medicine, rather than a stand-alone medication, said Dr Andrea Trescot, physician, The Pain and Headache Center, Eagle River, Alaska. Some cancer patients have reached maximum efficacy with opioids, so additional options are always sought, she said. Trescot noted that she liked the concept of the oral spray, especially for patients having oral or esophageal cancers who cannot swallow medications.
The market is anxious to have another nonopioid agent for cancer pain, agreed Dr Eric Grigsby, founder, Neurovations, a Napa, California-based clinical research company in pain management and neuroscience. Cannabinoids are not viewed as great analgesics when used alone, but they make sense as add-on therapy, he said. Grigsby added, though, he would like additional information before treating patients on how the drug acts in tangent with opioids in affecting opioid-related side effects such as hypoxemia or respiratory depressions.
Sativex does not cause opioid side effects such as hypoxemia and respiratory depression, said CEO Justin Gover. Since the drug is planned in all trials as an add-on treatment to opioids, safety information has already been generated about the coadministration, he added, and more data will be generated in the Phase III trials.
“I personally think [Sativex] is a good medication,” said Dr Emil Annabi, director, pain management, Arizona Health Science Center, adding he would prescribe it in his practice.
Considering Sativex’s good side-effect profile, it will be a good adjunct to current therapy but is not potent enough to replace traditional opioids, said Dr Brian Durkin, director, Center for Pain Management, Stony Brook, New York, and Dr James Cleary, director, palliative medicine, University of Wisconsin Hospital and Clinics.
Sativex will do well in the market, said Dr Raed Rahman, medical director, The Pain Management Services, Cancer Treatment Centers of America, Chicago, Illinois. He noted that a recent survey of 1,000 cancer patients and caregivers found that one in four patients and caregivers are dissatisfied with their cancer care. In the study, 64% of patients described pain management as an important part of their treatment.
Both the Drug Enforcement Administration (DEA) and the FDA have publicly expressed interest in cannabinoids in the prescription field, Gover said.
Drug scheduling and abuse
While Sativex is unapproved in the US, it remains a Schedule I substance (deemed as having no medical use), so GW and the DEA work closely to ensure that trial sites are licensed appropriately, Gover said. An FDA approval would lead to DEA scheduling, so the drug would move to Schedule II or III depending on FDA/DEA assessment, he added.
Cancer pain patients take opioids that are Schedule II or III, Gover noted, so if Sativex is approved, “there is no reason to consider that [Sativex’s] uptake will be restricted by its scheduling,” he said.
As long as the DEA schedules Sativex as a Schedule II or III product, the abuse potential may be mitigated, Rahman said. The agency and the FDA may have to consider abuse potential versus better quality of life, he added.
GW and investigators evaluated Sativex’s abuse potential [Schoedel, et al. Human Psychopharmacology: Clinical and Experimental. April 2011; Vol. 26 (3): 224-236.] at three dose levels: four consecutive sprays, eight consecutive sprays, and 16 consecutive sprays of 10.8mg, 21.6mg and 43.2mg THC, respectively, versus placebo and two doses of AbbVie’s (NYSE:ABBV) Marinol (dronabinol) capsules. Marinol is a Schedule III substance, and the trial was a randomized, double-blind, crossover study in 23 recreational cannabis users.
Marinol and Sativex had significant abuse potential at higher doses compared with placebo, the study found. Sativex showed similar or slightly less abuse potential compared to Marinol.
On the abuse spectrum, Sativex is on the lower end, said Dr Edgar Ross, director, Pain Management Center, Brigham and Women's Hospital, Boston, Massachusetts. Sativex has minimal abuse potential, similar to Marinol, Durkin agreed. The therapy’s risk-benefit aspect of possible abuse will be weighed against the concept of better, nonopioid pain control with a possible minimization on opioid dependence. The Phase IIb study indicated that even if patients had access to higher doses, they chose the lower dose, Trescot said, which indicates low abuse potential.
For abuse to actually be seen, though, Ross noted that a study of thousands of patients would have to be done. There have been few, if any, bona fide cases of Sativex abuse in either clinical trials or in postmarketing experience in more than 20 countries in which the product is marketed for multiple sclerosis spasticity, said a person familiar. Sativex was first approved in Canada in 2005 and is now also allowed for use in the UK, Spain, and New Zealand to treat spasticity due to multiple sclerosis, according to the company’s website.
Sativex’s molecules have a long history of abuse, noted a US-based Phase IIb investigator. “Despite the very reassuring experience thus far, it is likely that a subpopulation will abuse it,” he said. Sativex should be Schedule II, he added.
The possibility of abuse is present, since Sativex penetrates the central nervous system, Annabi agreed. That being said, every opioid marketed also has abuse potential, he added. To mitigate abuse, the FDA will likely emphasize the label needs to read for cancer pain only, he noted.
“Whilst there is no evidence to date from prescription use that Sativex is abused, it will inevitably be deemed in the US to have some abuse potential due to its cannabis origin,” Gover said. “As part of our US development program, we have conducted formal human and animal abuse liability studies.”
Since patients using Marinol or Sativex test positive for THC in their urine, physicians may be wary of prescribing Sativex not knowing for sure if patients are also illegally using marijuana, Grigsby said. Ross, however, did not think that THC in the urine would be a significant concern for cancer patients.
Patients taking Sativex have THC in their urine, Gover said, but for the thousands of patients taking Sativex in Europe, the company has “never, as far as we are aware, encountered a problem with a physician hesitating to prescribe the fact that it produces THC in urine”.
GW Pharmaceuticals’ market cap is GBP 85.6m (USD 129.1m).
by Jennifer C Smith-Parker in Washington, DC