27 Juni 2005

Sativex – Novel cannabis derived treatment for MS pain now available in Canada by prescription

Also: Multiple Sclerosis Society of Canada comment and Medical Update Memo

TORONTO, Ontario – Sativex® (Cannabis sativa L. extract), the only adjunctive treatment for symptomatic relief of neuropathic pain in adults with multiple sclerosis (MS), is now available in Canada. The novel treatment can now be obtained by prescription through Canadian pharmacies. In April 2005, Canada became the first country in the world to approve Sativex, an effective and safe cannabis derived prescription medicine.
 
Health Canada has approved Sativex with conditions, under the Notice of Compliance with Conditions (NOC/c) policy.  This authorization reflects the promising nature of the clinical evidence which will be confirmed with further studies.  Products approved under Health Canada’s NOC/c policy, have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment for the approved use.
 
“Effective pain control and management are extremely important in a disease like MS,” said Dr. Allan Gordon, Neurologist and Director of the Wasser Pain Management Centre, and of the Edward Bronfman Family Foundation MS Research Clinic at Mount Sinai Hospital, Toronto, Ontario. “The availability of Sativex addresses the great demand for an effective treatment option in the field of neuropathic pain in MS.  Many patients, including some in my own practice, report using cannabis for relief of their pain.  People with MS and neuropathic pain should speak to their doctor to determine whether Sativex is an appropriate option for them.”
 
How it works
Sativex is administered through a spray pump under the tongue or on the inside of the cheek, providing reliable, self-administered pain relief.  The spray formulation allows for more flexible dosing than an oral tablet, well suited to the variable nature of neuropathic pain experienced by people with MS.
 
“Sativex will be welcomed by the Canadian MS community,” said Dr. William J. McIlroy, National Medical Advisor, Multiple Sclerosis Society of Canada. “Neuropathic pain associated with MS is often under treated and under controlled. The availability of Sativex will now allow people living with MS and neuropathic pain a new treatment option to address one of the more debilitating symptoms associated with the disease.”
 
Principal components
Sativex is a product resulting from the pioneering research efforts of UK-based GW Pharmaceuticals plc and is marketed in Canada by Bayer HealthCare, Pharmaceuticals Division.
 
Its principal active cannabinoid components are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).(1)  The ratio of THC to CBD in Sativex is
2.7 mg : 2.5 mg per spray, ensuring a standardized dose is delivered each time it is used.
 
Neuropathic pain
Pain is a common symptom of MS occurring in up to 86 per cent of people with MS.(2) Neuropathic or nerve pain can occur spontaneously or can be provoked by touch, temperature or movement. It is estimated that 50 per cent of people with MS suffer from chronic neuropathic pain.(3),(4),(5) The most common descriptions of neuropathic pain are of freezing, cold or burning sensations usually of the limbs and most often of the lower extremities.(6) Many individuals with neuropathic pain respond inadequately to current treatment options.(7),(8)
 
Data demonstrates efficacy1
While there is no complete cure for MS or neuropathic pain, a double-blind placebo controlled parallel group study demonstrated that Sativex provided significantly greater pain relief than placebo. Sativex also significantly reduced pain-related sleep disturbance.
 
Sativex and side-effects1
In clinical trials, the most frequent side-effects included nausea, fatigue, dizziness and application site reactions. Side-effects were usually mild or moderate in severity and often resolved with down-titration or interruption of treatment.
 
Multiple sclerosis (MS) in Canada (9)
MS is a disease of the central nervous system and is the most common neurological disease affecting young adults in Canada. Approximately 50,000 Canadian men and women have the disease and each day approximately three more people are diagnosed.  MS is most often diagnosed in people between the ages of 20 to 40 years of age.
 
About Bayer HealthCare AG
Bayer HealthCare AG, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the health care and medical products industry.  In 2004, the Bayer HealthCare subgroup generated sales amounting to some 8.5 billion Euro.

The company combines the global activities of the divisions Animal Health, Biological Products, Consumer Care, Diabetes Care, Diagnostics and Pharmaceuticals. Bayer HealthCare employed 35,300 people worldwide in 2004.

Bayer HealthCare’s aim is to discover and manufacture innovative products that will improve human and animal health worldwide.  The products enhance well-being and quality of life by diagnosing, preventing and treating disease.
 
About GW Pharmaceuticals plc
GW Pharmaceuticals plc is licensed by the UK Home Office to undertake a pharmaceutical research and development program to develop non-smoked cannabis-based prescription medicines. GW’s shares are publicly traded on AiM, a market on the London Stock Exchange. 
 
Full details of GW and the company’s clinical trials program can be found at www.gwpharm.com. GW’s clinical research program is being carried out by a team of pharmaceutical professionals experienced in drug development and, in particular, the development of plant-based medicines and drug delivery systems.
 
References:
(1) Sativex Product Monograph – April 2005
(2) Ehde DM, et al.  Multiple Sclerosis 2003; 9; 605-611.
(3) Archibald CJ, et al. Pain 1994; 58:89-93.
(4) Sketris IS, et al. Clinical Therapeutics 1996; 18(2):303-318.
(5) Moulin DE, et al. Neurology 1988;38:1830-1834.
(6) Multiple Sclerosis International Federation
(7) Harden N and Cohen M.  Journal of Pain Symptom Management 2003; 25 (5 Suppl): S12-S17.
(8) New Directions in Neuropathic Pain: Focusing Treatment on Symptoms and Mechanisms.  Royal Society of Medicine Press Ltd.: 2000.
(9) http://www.mssociety.ca/en/information/faq.htm

Multiple Sclerosis Society of Canada comment
The Multiple Sclerosis Society of Canada welcomes the availability of Sativex, which will provide people with MS and their physicians another choice in treating pain, which is a common symptom of the disease. “Having available another way to manage pain is encouraging news,” said Dr. William J. McIlroy, national medical advisor.

Medical Update Memo – June 20, 2005 (Updated)

Details
Health Canada approval of Sativex on April 19 made Canada the first county in the world in which the cannabis-based spray is available as a prescribed treatment for MS-related pain. On June 20, Bayer Canada announced that Sativex had become available for prescription. Sativex is sprayed under the tongue or on the inside of the cheek from a dispenser that is programmed to deliver a pre-selected dosage. It is described as a whole marijuana plant extract. It includes two components of marijuana tetrahydrocannabinol (THC) and cannabidiol.

According to Bayer Canada, the cost of Sativex per vial is $124.95 (base price). Each vial contains approximately 51 sprays. The average dose per day is five sprays at an average cost of $12.25 per day. Based on this dosage, the base cost would be approximately $4,475 (the retail cost will be more depending upon pharmacy dispensing fees and other factors). Since the dosage is variable, to a maximum of 14 sprays per day, costs would increase or decrease accordingly. Private or group drug insurance plans may cover all or some of the cost. Sativex has yet to be approved for reimbursement by any federal, provincial or territorial drug program.

According to Bayer Canada, people who are prescribed Sativex should be aware that current regulations do not allow it to be taken out of Canada since it is a cannabis-based product and, therefore, a controlled substance.

Health Canada has approved Sativex with conditions, under the Notice of Compliance with Conditions (NOC/c) policy. This authorization reflects the promising nature of the clinical evidence to be confirmed with further studies. Products approved under Health Canada’s NOC/c policy have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment for the approved use.

Health Canada approval was based on the results from a small, four-week clinical trial carried out in Great Britain by GW Pharmaceuticals, the company that developed Sativex. The study involved 66 people with MS at a research centre in Britain. Participants had central neuropathic pain because of MS. Half of the group received Sativex in a spray dispenser and the other half received a sham (placebo) spray in a similar dispenser.

The primary outcome measure was to measure the effectiveness of Sativex in relieving central neuropathic pain compared to placebo. Secondary measures included sleep disturbance, participants’ perception of their condition at the end of treatment and other quality of life assessments.

Study results and possible mechanism of action Participants in the Sativex group used fewer sprays per day than did the placebo group. In addition, individuals in the treated group reported they experienced pain relief, had less sleep disturbance and felt their condition had improved.

There were more side effects in the Sativex-treated group versus the placebo group. When combining data from this and several other phase three clinical trials (total of 166 participants), the most common side effect of Sativex was dizziness which occurred in 41.6% of treated participants versus 13% of participants in the placebo group. There was also more nausea in the treated group (10.2%) than in the placebo group (7.4%) and more fatigue in the treated group (11.4%) versus the placebo group (5.6%). Side effects tended to diminish overtime.

Cannabinoids is the name given to more than 60 related chemicals in the marijuana plant. Cannabinoids appear to bind to receptor molecules on the surface of neurons in the brain and spinal cord. Through a complex process, cannabinoids appear to prevent neurons from becoming overactive, which leads to the neuropathic pain sometimes experienced in MS. Neuropathic pain results directly from damage to the nerves.

A number of clinical trials have been carried out in the past five years to test the effectiveness and safety of marijuana as a treatment for MS pain and spasticity. Some studies used the smoked variety of marijuana, while others used extracts of the plant delivered in various ways. The outcome of the largest study, which looked at spasticity, was mixed in that while those on active treatment did not have an objective improvement as measured by a standardized scale, treated participants reported improvements in walking speed, another measure of spasticity, and symptoms of spasticity, muscle spasms, sleep and pain.

Pain as a symptom of MS
Up to 80 percent of people with MS report some type of pain. A recent study of pain at Dalhousie University involving 85 people with MS found that 53 percent of people with MS experienced pain during the study period and that 17 percent reported continuous pain. Of those reporting pain, 65 percent took medication to control pain, with 90 percent reporting that their pain could be controlled about half of the time. Study participants who reported pain had poorer overall mental health than people who were pain free or who had well-controlled pain. There is a wide variety of pain associated with MS from a range of causes: generalized pain, muscle spasms, trigeminal neuralgia (shooting pain in the face), painful sensations in the legs, feet and hands.

Background and status of marijuana as a therapy in Canada Marijuana’s role as a medication is complex and controversial. It was used as a medication in the nineteen century but was outlawed in most western countries in the early to mid twentieth century. Recently in Canada, the federal government developed a medicinal marijuana program, which allows people who meet certain criteria to have permits to possess and grow marijuana. MS is among the conditions for which a permit can be applied. In some cases, Health Canada will provide marijuana to people who hold permits. Details about how to apply for permits are available at the Health Canada website: www.hc-sc.gc.ca; then click on Health Protection and then Medical Marijuana. Information is also available by calling the Health Canada Cannabis Medical Access Office toll-free: 1-866-337-7705 or 613 954-6540.

It is not known if the approval of Sativex will result in any changes to the Health Canada Marijuana Medical Access Program. One issue that has arisen from the Health Canada medical marijuana is that some physician organizations have advised their members not to prescribe marijuana because of the lack of information about optimum prescribing and potential legal issues.

Other cannabis-based drugs are Marinol® (dronabinol) and Cesamet® (nabilone). Both are synthetic versions of THC in tablet form. They are used primarily by people with cancer and AIDS to treat nausea related to certain treatments and to stimulate the appetite.

(Cf. news from April 21, 2005.)

Source: Bayer HealthCare press release and Medical Update Memo of Multiple Sclerosis Society of Canada June 20, 2005

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