GW Pharmaceuticals and Otsuka Pharmaceutical Development & Commercialization said today their Phase III experimental cannabinoid drug Sativex® missed its primary endpoint in the first of three Phase III trials, showing no statistically significant difference from placebo in easing the pain of advanced cancer patients.

The trial was designed to assess whether Sativex, when used as adjunctive treatment to optimized chronic opioid therapy, could effectively treat pain in patients with advanced cancer who experienced inadequate analgesia.

The trial’s primary efficacy measure was a patient assessment of pain using a 0-to-10 Numeric Rating Scale (NRS) whose data was analyzed primarily on the basis of percent improvement from baseline. Improvement was also analyzed using a cumulative proportion of responders analysis (CPRA).

Neither analysis showed a statistically significant difference between Sativex and placebo. GW said efficacy data from U.S. sites showed more positive trends than those in non-U.S. sites, consistent with data from the Phase IIb trial—but the difference was not statistically significant.

Sativex was well tolerated by patients, the companies said, with only two adverse events reported at greater than 10% patients taking the experimental drug: Neoplasm progression (16% on Sativex vs 18% on placebo) and somnolence (12% on Sativex vs 4% on placebo). The third most-frequent event was dizziness (8% on Sativex vs 5% on placebo). A total of 38 patients (19%) withdrew due to adverse events on Sativex compared with 29 (15%) placebo users.

The Phase III trial assessed Sativex at a dose range of 3-to-10 sprays per day over five weeks, with an additional 5-to-14 day stabilization period at the beginning of the trial and a one-week follow-up at the end. A total 399 patients were recruited at sites in the U.S., Mexico, and Europe.

GW and Otsuka said they expected to generate better results later this year from the remaining two Phase III trials to support an NDA to the FDA.

The second Phase III pivotal trial, identical to the first, is expected to report top-line results in the second quarter of this year.  GW and Otsuka are also conducting a third Phase III trial, in which the effects of Sativex in treating opioid-resistant cancer pain will be studied on about 540 patients. The third Phase III trial differs in design from the first two trials, and is expected to generate results “towards the end of 2015,” the companies said.

“We believe that cannabinoid therapy offers a potentially novel approach as a co-analgesic to provide pain relief beyond opioid therapy, Prof. Marie Fallon, M.D., the trial’s principal investigator and professor of palliative care at University of Edinburgh, said in a statement.

Sativex previously completed a Phase IIb dose ranging study and Phase IIa study. Both studies produced more positive results, reporting that Sativex showed statistically significant improvements compared with placebo using the same primary measure as in the Phase III trial.

“Based upon the positive data seen in the Phase II program, we remain confident in the ability for Sativex to relieve cancer pain in this patient population,” GW CEO Justin Gover stated.

Sativex is the world’s first plant-derived cannabinoid prescription drug, already approved for the treatment of spasticity due to multiple sclerosis in 27 countries—but not in the U.S., where the company has submitted a Special Protocol Assessment request to the FDA for a proposed single Phase III study in that indication.

The drug won approval in MS spasticity in Europe following trials that employed a two-part “enriched” trial design to be used in the third Phase III study for cancer pain.








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