Nabiximols
Nabiximols (USAN, trade name Sativex) is a patented cannabinoid oromucosal mouth spray developed by the UK company GW Pharmaceuticals for multiple sclerosis (MS) patients, who can use it to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms. Nabiximols is distinct from all other pharmaceutically produced cannabinoids currently available because it is a mixture of compounds derived from Cannabis plants, rather than a mono-molecular synthetic product. The drug is a pharmaceutical product standardised in composition, formulation, and dose, although it is still effectively a tincture of the Cannabis plant. Its principal active cannabinoid components are the cannabinoids: tetrahydrocannabinol (THC) and cannabidiol (CBD). The product is formulated as an oromucosal spray which is administered by spraying into the mouth. Each spray delivers a near 1:1 ratio of CBD to THC, with a fixed dose of 2.7 mg THC and 2.5 mg CBD. Nabiximols is also being developed in Phase III trials as a potential treatment to alleviate pain due to cancer. It has also been researched in various models of peripheral and central neuropathic pain.
In May 2003 GW Pharmaceuticals and Bayer entered into an exclusive marketing agreement for GW’s cannabis-based medicinal extract product, to be marketed under the brand name Sativex. "Bayer has obtained exclusive rights to market Sativex in the UK. In addition, Bayer has the option for a limited period of time to negotiate the marketing rights in other countries in European Union and selected other countries around the world."
In April 2011, GW licensed to Novartis the rights to commercialise nabiximols in Asia (excluding China and Japan), Africa and the Middle East (excluding Israel).
Availability
In June 2010, the Medicines and Healthcare products Regulatory Agency of the United Kingdom licensed nabiximols as a prescription-only medicine for the treatment of spasticity due to multiple sclerosis. This regulatory authorization represents the world's first full regulatory approval for the medicine. The spray is being marketed in the UK by Bayer Schering Pharma. Many MS patients cannot receive nabiximols due to local National Health Service (NHS) resistance to its funding. but, in August 2014, the NHS in Wales agreed to fund Sativex for people with multiple sclerosis.
Nabiximols was also approved in Spain for MS spasticity in the second half of 2010 and was launched in that country in March 2011. It was approved in the Czech Republic in April 2011, in Germany in May 2011, in Denmark in June 2011 and in Sweden in January 2012 to MS patients who have not responded adequately to other medication for spasticity. It has also been recommended for approval in Italy and Austria with formal approvals expected in these countries during 2011. In Spain and other European markets (excluding the UK), nabiximols will be marketed by Almirall.
In Canada, nabiximols has been approved by Health Canada for the treatment of MS spasticity. It has also received a licence with conditions (NOC/c) for two additional uses: as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis, and also for pain due to cancer.
Nabiximols is available in a number of countries as an unlicensed medicine, which enables doctors to prescribe the product to individual patients who they consider may benefit. The product has been exported from the UK to a total of 28 countries to date.
In February 2007, GW and Otsuka Pharmaceutical announced an exclusive agreement for Otsuka to develop and market the drug in the United States. The first large scale US Phase IIb trial, Spray Trial, for cancer patients reported positive results in March 2010. GW and Otsuka have now commenced the Phase III development of nabiximols in cancer pain.
In 2013, France legalized the use of cannabinoids in medicine, Sativex is the first one to be sold under prescription.
Effectiveness
Of the two preliminary Phase III studies investigating the treatment of MS patients, one showed a reduction of spasticity of 1.2 points on the 0–10 points rating scale (versus 0.6 points under placebo), the other showed a reduction of 1.0 versus 0.8 points. Only the first study reached statistical significance. The Phase III approval study consisted of a run-in phase where the response of individuals to the drug was determined. The responders (42% of patients) showed a significant effect in the second, placebo controlled, phase of the trial. A 2009 meta-analysis of six studies found large variations of effectiveness, with a – statistically non-significant – trend towards a reduction of spasticity.
Side effects
In early clinical trials, nabiximols has generally been well tolerated. The most common adverse effects in Phase III trials were dizziness (25%), drowsiness (8.2%) and disorientation (4%). 12% of patients stopped taking the drug because of the side effects. No investigations regarding the potential for dependence are available, but such a potential is unlikely considering the pharmacological properties of the two components.
Controversy
GW Pharmaceuticals were issued a unique license to cultivate cannabis for the manufacturing of Sativex in the UK, granting them the sole legal right to research in aerosolized cannabis derived therapeutics, which in April 2013 became commercially viable when the UK Government scheduled the Sativex formulation to part IV of the UK Drugs Act.
