BioWorld International Correspondent

LONDON - GW Pharmaceuticals plc, which is developing cannabis-based compounds to treat the symptoms of multiple sclerosis, says it has a growing base of evidence that the compounds also are modifying the progression of the disease. It now is working to design a trial to test that.

The evidence come from long-term extension studies to the acute Phase III trials of GW's compound, Sativex, which is awaiting regulatory approval in the UK. If approved, Sativex would be the first cannabis-based medicine to reach the market.

"In all the acute studies we have done, we've had an option for patients to progress into long-term extension, and 75 percent have elected to continue," said Philip Robson, medical director. That has created what he called a "real world" body of safety and efficacy data.

There was significant improvement in spasticity scoring in the acute phase of the study, and the improvement has been sustained in the extension study.

"Remember, this is a progressive, remorseless disease - in other words, the actual condition is not going to be improving," Robson said at an analyst's meeting in London last week. "This was a surprising, and to me remarkable finding."

Similarly, the significant improvements in pain, spasm and bladder problems in the acute Phase III studies have been sustained in the extension study.

Robson stressed that the extension is an open study with no placebo arm, but still, it is "extremely impressive and reassuring," he said.

In all, Sativex has been tested in 1,200 subjects, and there are 700 patient years of data. The drug has achieved positive results in four Phase III studies, and five more are due to complete this year.

Sativex is a nasally administered spray, containing both tetrahydrocannabinol and cannabinol, constituents of cannabis that cause the "high" in recreational drug use.

Patients self-administer the drug according to need, and Robson said that that issue raised the question of whether the sustained improvements in the extended trial were at the cost of increasing dose.

"We have monitored patients - the average is 11 sprays per day, and it is not going up," he said.

The aim of a medical user is to avoid intoxication, and Robson said over time patients have gotten even better at achieving the correct dose, separating symptom improvement from intoxication.

A study with 11 patients, designed to evaluate if they experienced withdrawal symptoms when the treatment was interrupted, also was reassuring, Robson said. "Seven of 11 had no effects, four did have effects, but there was no recognizable syndrome," he said.

The findings, plus animal work demonstrating cannabis has an impact on progression in mouse models of multiple sclerosis; a recent study that reported patients on active treatment had fewer hospital admissions due to relapses; and anecdotal evidence that people feel the disease "slow," is encouraging GW to carry out a formal trial.

GW applied for UK approval of Sativex in March. It submitted responses to questions at the end of 2003 and expects approval in the second half of 2004 in MS and neuropathic pain.

Before it can go on the market as a prescribed drug, the product will need to be rescheduled under the UK's Misuse of Drugs Act. Geoffrey Guy, executive chairman, said the UK government has indicated it intends to make the change.

Sativex is licensed to Bayer Healthcare in the UK and Canada, and the dossier will be submitted in Canada soon. Bayer has options on other territories, but GW says the strategy is to capture the lion's share of the product's value by waiting until it has UK approval before licensing elsewhere. It also has further Phase III trials due to report in 2004, and expects those to pave the way for extensions to the label. The company has had talks with U.S. regulators and says it will turn its attention to meeting requirements for U.S. registration once Sativex is approved in the UK.

GW grows cannabis at an undisclosed location, and says it has all the production, manufacturing, supply chain and marketing teams ready for a UK launch later this year.

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