Bayer has secured exclusive rights to market Sativex in the UK with the option to extend this to other countries in Europe and countries such as Canada, where Sativex received regulatory approval in 2005 for treatment of neuropathic pain associated with MS. Sativex and a related tetrahydrocannabinol (THC) medicine are also undergoing phase III trials for the relief of cancer pain. If this indication is approved, Bayer has an option to market these drugs for neuropathic-related cancer pain.

In February 2007, GW Pharmaceuticals entered into a long-term research and development alliance on medicinal cannabinoids with Otsuka Pharmaceutical, which gives Otsuka exclusive rights to develop and market Sativex in the US. The companies will jointly oversee clinical development and regulatory activities in the US. Having secured FDA approval to conduct trials of Sativex in patients with advanced cancer, whose pain is unrelieved by opioids, the companies are now planning the first US efficacy trial of Sativex in neuropathic-related cancer pain.

CANNABIS-BASED MEDICINES
Estimates suggest that between 10% and 30% of MS patients in Europe smoke cannabis to ease the pain and disabling symptoms of the disease. This activity is illegal and patients run the risk of prosecution. In the UK, cannabis-based medicines were in fact outlawed in 1968 after legislation banned doctors from prescribing tincture of cannabis. This preparation contained high concentrations of the active THC psychotropic ingredient and was popular among recreational cannabis users.

The UK Government gave GW Pharmaceuticals special permission to investigate medicines derived from cannabis and has indicated that the law will be changed to allow doctors to prescribe them if approved by the MHRA. This would represent a major step forward for MS patients as for the first time they would have access to safe and effective cannabis-derived drugs on prescription.

Sativex is a cannabis extract containing tetranabinex (THC) and nabidiolex (cannabidiol - CBD) as its principal component. It does not contain the active substance found in recreational cannabis and so patients taking Sativex will not become intoxicated. Sativex is administered by means of a spray into the mouth rather than smoked.

To meet demands for this innovative drug, GW Pharmaceuticals has increased production of cannabis at its fortified greenhouses to 60t/y.

CLINICAL TRIALS ON SATIVEX POINT TO GOOD EFFICACY AND SAFETY
Phase III placebo-controlled trials in about 350 patients with MS have shown that administration of Sativex as a sublingual spray is a safe and effective treatment for symptom relief. Compared with placebo, significantly more patients in the Sativex treatment arm experienced reduced neuropathic pain, spasticity and sleep disturbances.

Further phase III data on 189 MS patients, released in June 2004, supports the earlier registration trial data. Again, treatment with Sativex produced a statistically significant improvement over placebo in spasticity, the primary endpoint, (p <0.05). Other secondary endpoints, such as the Ashworth scale, also favoured Sativex over placebo. Overall, this new data has shown that Sativex produces treatment effects over and above those achieved with existing medications, which patients were allowed to continue while taking part in the Sativex trial.

Recent data from an independent study (CAMS) were presented at the British Association Science Festival. They showed that when administered over 52 weeks to MS patients, treatment with cannabinoids proved more effective in alleviating muscle stiffness than during a shorter, 15-week period. In the initial 15-week trial, the results of which were published in 2003, patients reported relief in muscle stiffness, rigidity and mobility, but these findings could not be independently confirmed by physiotherapists.

Of the 667 patients who participated in the short-term phase of CAMS, more than 500 continued to receive treatment for up to 52 weeks. Patients were given either whole cannabis extract, capsules containing a synthetic version of THC, or placebo. While the CAMS trial did not involve the use of Sativex, the encouraging results nonetheless help to reinforce the medical case for Sativex in MS.

Additional trials are also under way to assess the effectiveness of Sativex in treating cancer pain and spinal cord injury. Anecdotal evidence suggests that Sativex and related compounds can dull severe pain while allowing patients to perform daily activities.

TREATMENT OF SEVERE NEUROPATHIC PAIN
Neuropathic pain, which is frequently chronic, arises when neurones in the brain or peripheral nervous system become hyper-sensitised and generate abnormal or prolonged impulses. There are many causes of neuropathic pain including diabetic neuropathy, post-herpetic neuralgia, fibromyalgia, multiple sclerosis and cancer. Around 40% of cancer patients suffer some degree of neuropathic pain.

Severe neuropathic pain has proved difficult to treat and evidence suggests that none of the available drugs, mainly opioids, is effective in more than 50% of patients. Thus, it represents an area of significant unmet clinical need. The encouraging data from the Sativex phase III registration trials in multiple sclerosis patients suggest cannabis-derived medicines may have a valuable place in this sector of the pain market.

MARKETING COMMENTARY
In Europe alone there are some 500,000 MS patients on top of the 4 million experiencing neuropathic pain. This fact, together with a market poorly served by currently available drugs, presents an excellent opportunity for Sativex if the encouraging results seen in multiple sclerosis are reproduced in other patient groups. Regulatory approval of Sativex will set an important precedent for the use of cannabis-derived drugs.

Source: Drug Development Technology, 2007
http://www.drugdevelopment-technology.com/projects/sativex/