BioWorld International Correspondent
LONDON - GW Pharmaceuticals plc lost the battle to register its cannabis-based medicine, Sativex, for the treatment of spasticity in multiple sclerosis on the basis of the existing data file, but won the war by convincing regulators there are no objective endpoints in the indication.
The upshot is that the company needs only to confirm the results of the trial in a second Phase III study. GW started such a trial in December when it launched the appeal against the refusal to grant Sativex a UK license, and that will report early in 2006.
News that the Committee of Safety on Medicines would turn down the appeal leaked last week, prompting an 18 percent fall in the share price. That was compounded by a further 14.5 pence fall to 81 pence when the formal announcement was made June 10.
Geoffrey Guy, executive chairman, told BioWorld International that while it was disappointing to lose the appeal, getting agreement on the endpoint for a second Phase III trial was significant.
"The issue was whether you could measure improvements in spasticity objectively, or if the endpoints should be based on patients' own assessments. The world's most senior experts said we had the correct endpoints, and now the regulators have accepted there are no objective measures," he said.
Some additional patient-assessed endpoints have been added to the ongoing Phase III trial to augment the data. In the Phase III trial that formed the centerpiece of the original submission, 40 percent of patients experienced 30 percent or greater improvement in spasticity, according to their own assessment. But using the Ashworth scale, a measure based on physicians' observations, the assessments of spasticity were in favor of Sativex but did not reach statistical significance.
That led UK regulators to conclude that while there were no safety or quality issues with the cannabis-based nasal spray, they were not convinced the data were clinically relevant. Following the appeal hearing in which it heard presentations from a number of experts in favor of the approval of Sativex, the Medicines Commission said the evidence of efficacy "is not yet sufficiently compelling."
One of the experts, Mike Barnes said he was "deeply saddened" by the failure of the appeal.
"It is my view that there is excellent clinical evidence to support regulatory approval of Sativex in the UK," said Barnes, who is president of the World Federation of Neuro-rehabilitation and professor of neurological rehabilitation at the University of Newcastle. "I am very disappointed that the Medicines Commission did not follow the recommendation of myself and other leading experts in the treatment of MS. People with MS have considerable unmet medical needs."
Since Sativex was refused a license in the UK for treating spasticity in MS, it has been approved in Canada for treating neuropathic pain caused by the disease, and the market launch is imminent.
GW followed the advice of UK regulators in applying for approval of Sativex in spasticity rather than neuropathic pain. "We wasted two years. All our neuropathic pain data met European guidelines in every respect but one, which was that the Phase III studies were not long enough. Rather than re-doing them at the required length of 12 weeks, we were persuaded to switch resources to spasticity," Guy said.
The 12-week neuropathic pain trial is under way, and expected to report before the end of 2005. GW has positive results in cancer pain, also. With £16.2 million (US$29.2 million) in cash at the end of May, Guy said Salisbury-based GW has sufficient funds to continue its research program. It soon will have revenues from Canada, where it expects to get further approvals.
The company is seeking an investigational new drug application meeting and hopes the weight of existing data will persuade the FDA to let it commence U.S. development at Phase IIb. Guy said Sativex could defuse the current controversy in the U.S. over the medical use of marijuana.
Similarly, he said that the second refusal of a license is an embarrassment for the UK government, which would welcome the availability of a prescription version of cannabis for treating defined problems, based on formal clinical trials.
"We represent government policy on this issue," Guy said.