BioWorld International Correspondent
LONDON - Shares in GW Pharmaceuticals plc fell 27 pence to 65 pence after the company was forced to withdraw the European submission of Sativex in treating spasticity in multiple sclerosis and conduct another trial.
Although sounding sanguine when he discussed the withdrawal with analysts, CEO Justin Gover argued the decision not to approve the cannabis-derived treatment was a "technical" one. It did not call into question the quality, safety or efficacy of the drug.
Mike Barnes, president of the World Federation of Neuro-rehabilitation, and professor of neurological rehabilitation at Newcastle University, went much further, accusing the UK Medicines and Health Products Regulatory Agency (MHRA) of taking a "bureaucratic approach."
"I personally think [Sativex] should have been approved [last] week," he said in a conference call, adding, "I'm very, very convinced of the efficacy data. The data on spasticity is in excess of the data on any other anti-spasticity drugs." Barnes, who has been involved in the development of other anti-spasticity drugs, has no links to GW Pharma.
At issue is the fact that the benefit obtained by those who respond in any way to the treatment is masked by the mean improvement across the whole of the patient population, which includes nonresponders. However, it is possible to identify patients who have responded within four weeks of treatment starting. The MHRA has asked for a trial in which responders are first identified and then randomized into treatment and nontreatment groups to confirm that the benefit is greater than placebo when responders only are treated.
Stephen Wright, GW's R&D Director pointed out that the MHRA agrees there are no quality or safety issues, that the data confirmed benefit in multiple sclerosis, and are in principle acceptable. "We could not have anticipated this kind of study would be required without having gone through the process to date. It is also clear that if the trial is positive we will get approval."
The Salisbury, UK-based company was planning to carry out a trial in responders only and Wright said the company expects to recruit the first patient in October. The trial is within the scope of the existing R&D budget.
Wright said the decision to withdraw will make no difference to the development timetable in other indications, including the treatment of pain in multiple sclerosis, or to a U.S. study in cancer pain, due to start in August.
The patients treated in the spasticity trial all had multiple sclerosis for at least 15 years, and were refractory to any other treatments. Many were unable to walk. The end point was patients' self-reported assessment of the severity of spasticity, supported by whether improvements made it easier to look after them, as assessed by caregivers.
Given the advanced stage of the disease, a 20 percent reduction in symptoms is considered clinically relevant, a 30 percent reduction as much improved. In the trial 35 percent of refractory patients had a 30 percent plus response, 50 percent had a 20 percent response.
"For many patients, really small improvements make a big difference," Gover said. "Some say a 10 percent improvement [in symptoms] really matters."
Sativex is available on a named patient basis in the UK, and Barnes pointed out that with 1,250 patients prescribed the drug currently, the regulators are out of step with clinicians in the field. "It is a remarkably safe medicine, with a very small risk of side effects in nonresponders."
He added that the decision to request a further trial shows, "A marked lack of care for patients and carers by the regulators."