There is now conclusive and reassuring evidence of the cannnabis-based treatment Sativex’s tolerability and effectiveness in reducing spasticity and related symptoms in multiple sclerosis, according to studies reported at the ECTRIMS/ACTRIMS meeting in Amsterdam.
This positive news comes at the end of a year in which Spain, Germany, the Czech Republic and Denmark joined the UK in giving the nod to Sativex (delta-9-tetrahydrocannabinol and cannabidiol). The treatment was developed by GW Pharmaceuticals and it is marketed in Europe outside the UK by Almirall; Bayer sells Sativex in the UK, while Novartis has been signed up as a partner for Australia andNew Zealand, Asia (excluding Japan, China and Hong Kong), the MiddleEast (excluding Israel/Palestine) and Africa.
Despite the excitement about developments in disease-modifying therapy that were announced at the Amsterdam meeting, symptomatic treatment also continues to be essential for people with MS. Patients experience a variety of distressing symptoms, but spasticity is one of the most common, affecting up to two-thirds of patients in a recent Spanish study. Spasticity not only has serious effects on MS patients’ quality of life, it is also expensive, costing some 15,000 euros per patient per year.
According to Professor Derek Wade, Oxford, UK: “The basic message is that Sativex has probably been more thoroughly studied that any, or indeed all, the other drug treatments for spasticity in people with MS.” He explained that Sativex’s indication in MS spasticity follows a clinical programme involving more than 1,500 patients, who participated in 15 Phase III randomised controlled trials.
It is sprayed into the mouth, and patients can use up to a maximum of 12 sprays a day. Since not all patients respond to Sativex, the indication specifies that it should be used only if spasticity-related symptoms improve significantly during an initial trial of the therapy. Further European approvals for Sativex in MS spasticity are expected by the end of 2012 and in the USA, in partnership with Otsuka Pharmaceuticals, GW Pharma has begun a Phase III programme for Sativex in the treatment of pain in patients with advanced cancer, but a future indication in MS spasticity seems likely.
Speaking in Amsterdam, Stephen Wright, R&D director at GW Pharma, said: “We certainly aim to have discussions to open an investigation programme in the USA in spasticity due to MS. This will follow on from the initial US cancer pain indication.”
Sativex is only the latest of many plant-based medicines to enter the clinic. But the agent has had to overcome special hurdles to gain approval. Cannabis is a controlled drug, and there have been worries about possible abuse and psychiatric side effects in patients treated with Sativex.
Side effects transient
Prof Wade was probably the first neurologist to use Sativex in patients. His clinical experience over more than a decade reflects findings in clinical trials and safety studies, where the most common side effects were dizziness, fatigue and sleepiness. He said: “Most side effects are mild to moderate and very transient. Rates of disorientation and reduced concentration are fairly low at 4%-8%, which is probably not that much different from other [anti-spasticity] drugs such as baclofen. In our experience, we have never seen any patient with what might be considered a psychiatric side effect.”
Prof Wade noted that Sativex’s greater tolerability compared to herbal cannabis is probably explained by the much lower peak blood levels of tetrahydrocannabinol and slower onset of effect seen with the agent. “You should not generalise side effects seen in recreational users to patients who use Sativex medically,” he said.
Other reassuring evidence comes from a recently-published placebo-controlled study of MS patients randomised to sudden withdrawal of Sativex after a mean of 3.6 years treatment. There was no evidence of withdrawal syndrome or physiological dependence in these patients, most of whom needed to restart treatment because their symptoms recurred.
Prof Wade concluded: “Sativex is not a panacea or miracle cure, but it has advantages in its beneficial effects not only on spasticity, but also pain and sleep. There are no specific risks to be concerned about, and Sativex must have a role in managing spasticity in people with MS after the failure of other available oral medications.”