Sativex® confirms clinically relevant improvement in MS-induced spasticity
19.10.2012 12:36
The positive data from the MObility ImproVEments with Spasticity in Multiple Sclerosis (MOVE) 2 study presented at the ECTRIMS Congress support the use of Sativex® to reduce symptoms of moderate to severe spasticity due to multiple sclerosis (MSS). The new study data shows that 41 % patients who were treated with Sativex® and did not respond to other therapies showed a clinically relevant effect after just 3 months. The drug has proven to be a cost-effective treatment in Germany, where Almirall has made it available, as it has in Spain and Denmark.
Almirall SA (ALM) today announced that the results of the MObility ImproVEments with Spasticity in Multiple Sclerosis (MOVE) 2 observational study conducted in Germany with 300 participating patients showed that a one-month treatment with the oromucosal spray Sativex® (THC:CBD) moderately to severe MS-induced spasticity (MSS) reduced by at least 20 % in 4 of 10 patients who did not respond to other conventional therapies. After three months, an improvement of at least 30 % was observed. A total of 55 % patients who had participated since the start of the study continued treatment after the third month.
This prospective observational study was presented on October 11, 2012 at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Lyon, France.
“An improvement of at least 30 % after 3 months is considered clinically relevant on the Numerical Rating Scale (NRS). For patients, this means less sleep disturbances due to MS-related spasms, less pain, improved bladder function and fewer limitations in everyday activities. These findings from everyday clinical practice confirm or exceed the results from previous clinical studies of Sativex® and were even achieved with slightly lower average daily doses,” commented MOVE 2 lead investigator Professor Peter Flachenecker, Neurological Rehabilitation Center Quellenhof, Bad Wildbad, Germany.
MOVE 2 is a multicenter, prospective observational study involving 300 adult patients with moderate to severe MSS treated in 42 MS specialty clinics throughout Germany. The NRS average values of MS-indicated spasticity decreased by 25 % compared to the values before treatment with Sativex®, with 41 % patients showing an improvement of at least 30 % compared to baseline (from 6.7 to 3.2 in this subgroup; p<0.0001). The quality of life measurements (MS QoL-54 scale) at the check-up after three months also showed improvements compared to the values before the start of the study (p < 0.01).
Sativex® showed generally good tolerability. Adverse events were reported in 16.6 % of treated patients, most commonly including dizziness, fatigue and dizziness, but these were predominantly transient and mild to moderate in nature.
These findings are also supported by additional new data from Sativex® Data collections in the United Kingdom (n=493, retrospective data collection, average treatment duration of 18 months) and Spain (n=103, 6 months prospective follow-up study), which will also be presented at this congress.
The clinical relevance was not only proven in the MOVE 2 study: a recent publication by J. Slof shows that Sativex® represents a cost-effective treatment method[i]. When applying a Markov model[ii] From the perspective of payers in the German healthcare system, the incremental cost-effectiveness ratio was for Sativex® at €10,809. This is well below generally accepted cost-effectiveness thresholds, such as the £30,000 (€38,000) set by the UK's National Institute for Health and Clinical Excellence (NICE).
In Europe Sativex® for the treatment of MS-related spasticity in the United Kingdom, Spain, Germany and Denmark. The drug will soon be introduced in Italy, Austria, Iceland and Norway. In addition, the company has received regulatory approvals in Belgium, Sweden, the Netherlands, Portugal, the Czech Republic and Slovakia, where the product is scheduled to be launched in late 2012.
Except for MS-incident spasticity is Sativex®, a drug developed by GW Pharmaceuticals, also in Phase III clinical development for the treatment of cancer-related pain. Almirall has marketing rights for Europe (excluding the United Kingdom) and Mexico.
About the MOVE-2 study
MObility ImproVEments with Spasticity in Multiple Sclerosis (MOVE) 2 was a multicenter, prospective observational study involving 335 adult patients (300 of whom were evaluable) with moderate to severe MSS who were treated in 42 MS specialist clinics throughout Germany. The study was designed to test the effectiveness of Sativex® to be evaluated in daily clinical practice. Patients were assessed at baseline, one month, and three months using validated measures including the NRS, Barthel Index of Activities of Daily Living, and Ashworth Scale.
The effectiveness analysis after the one-month trial period of treatment in the patient population of 276 participants showed the following results:
237 (79 %) of the 300 evaluable patients who participated in the study continued treatment with Sativex® after the initial testing period. The improvements seen in these patients after one month of treatment were still noticeable or had improved three months after the start of the study:
After three months, the proportion of patients with MSS requiring home physiotherapy fell by a third, from 27.3 % to 17.8 %. Severe impairment in activities of daily living was reported by 25 % fewer patients, while the proportion of patients reporting severe and bothersome pain decreased by 15.5 %. Sativex® showed generally good tolerability. Adverse events similar to those reported in the clinical trials, such as dizziness and drowsiness, were reported, although these occurred in fewer cases. At the three-month follow-up, 55.3 % of the patients who had taken part in the study since the start decided to continue treatment with Sativex®.
About Sativex®
Sativex® is an endocannabinoid system modulator consisting of two active ingredients: THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol). The drug is developed and manufactured by GW Pharmaceuticals plc, UK. Almirall has marketing rights for Europe (excluding the UK) and Mexico.
Sativex® is indicated as a treatment for patients with moderate to severe spasticity due to multiple sclerosis (MS) who have not responded to other muscle relaxants and who have demonstrated significant improvement in spasticity symptoms during an initial trial period of treatment[iii]. Sativex® is effective in all types of MS and regardless of disability status (according to the Expanded Disability Status Scale, EDSS, a scoring system often used to classify and systematically assess the degree of disease in patients with multiple sclerosis).[iv]
The active ingredients contained in Sativex® are called cannabinoids. They come from the Cannabis Sativa plant, which is grown and processed under strictly controlled conditions. Cannabinoids react with the body's own cannabinoid receptors, including in the brain.[v] A receptor is a specific area in a brain cell to which certain substances bind for a limited period of time. This binding causes the cell to send out nerve impulses that ultimately cause a reduction in spasticity. This effect diminishes in patients on Sativex® address the symptoms of spasticity and help those affected to better cope with their everyday tasks.[vi]
Except for MS-incident spasticity is Sativex®, developed by GW Pharmaceuticals, is also in Phase III clinical development for the treatment of cancer-related pain.
Spasticity
An estimated 500,000 people live with MS in the five largest EU markets[vii]. Spasticity is a symptom described by patients and carers as muscle spasms, seizures, stiffness and/or limitation of movement and is one of the most common symptoms of MS, occurring in up to 75 % of sufferers over the course of the disease. Spasticity affects many aspects of MS patients' daily lives and is a major cause of their suffering and frequent disability.[viii]
About Almirall
Almirall is an international, innovation and research-oriented pharmaceutical company committed to health and promoting quality of life. Headquartered in Barcelona, Spain, the company conducts its own research and development and develops, produces and markets both its own and licensed medicines with the aim of improving people's health and well-being. Almirall focuses its research resources on therapeutic areas related to the treatment of lung, gastrointestinal and skin diseases and pain. Almirall products are currently available in over 70 countries on five continents. With the opening of the branch in Canada, Almirall is now directly represented with 13 of its own branches in Europe, Mexico and Canada.
i. Sativex® in multiple sclerosis spasticity: a cost-effectiveness model – Slof J et al, Expert Rev. Pharmacoecon. Outcomes 2 Res. 12(4), (2012))
ii. Markov models in medical decision making: a practical guide. – Sonnenberg FA, Beck JR. – Med Decis Making. Oct.-Dec. 1993;13(4):322-38.
iii. Patient information sheet
iv. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis – Novotna A. et al, European Journal of Neurology September 2011; 18(9):1122-31.
v. GW Pharmaceuticals: Cannabinoid Science: Mechanism of action. Available on. http://www.gwpharm.com/mechanism-of-action.aspx (Last accessed: April 26, 2012).
vi. GW Pharmaceuticals: Cannabinoid Science: Cannabinoid Compounds. Available on: http://www.gwpharm.com/types-compounds.aspx (Last accessed: April 26, 2012).
vii. Multiple Sclerosis International Association (MSIF): European Map of MS database. ©2010 EMSP, MSIF. Available on: http://www.europeanmapofms.org (Last accessed: August 11, 2010). The top five EU countries include: France, Germany, Italy, Spain and the United Kingdom.
viii. Rizzo MA et al. Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler 2004;10:589-595.
Source: Almirall