National Horizon Scanning Centre. Cladribine (Movectro) for multiple sclerosis; relapsing-remitting. April 2008

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1 Cladribine (Movectro) for multiple sclerosis; relapsing-remitting April 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research

2 Cladribine (Movectro) for multiple sclerosis; relapsing-remitting Target group Multiple sclerosis (MS); relapsing-remitting (RRMS). Technology description Cladribine (2-chlorodeoxyadenosine) is a deaminase-resistant deoxyadenosine analogue that selectively reduces lymphocyte counts 1. The antilymphocytic effects of the drug may reduce the autoimmune destruction of myelin. Cladribine is licensed as an intravenous (IV) preparation for hairy cell leukaemia and chronic lymphoblastic leukaemia in the UK. Innovation and/or advantages There are currently no oral treatments for MS, therefore if licensed cladribine would be one of the first non-injectable options for RRMS. Developer Merck Serono. Availability, launch or marketing dates, and licensing plans: In phase III clinical trials. NHS or Government priority area: This topic is relevant to the Long-term Conditions National Service Framework (2005). Relevant guidance NICE technology appraisal in development. Cannabinoids for the treatment of the symptoms of multiple sclerosis. Status: suspended (date of issue to be announced) 2. NICE technology appraisal. Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis (review date: June 2010) 3. NICE technology appraisal. Multiple sclerosis - beta interferon and glatiramer acetate NICE clinical guideline. Management of multiple sclerosis in primary and secondary care Clinical need and burden of disease Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Symptoms include fatigue, spasticity, bladder/bowel problems, ataxia, tremor, visual problems, pain, depression/anxiety, dysphagia, and sexual dysfunction 6. MS is the most common neurological disorder among young adults and causes considerable disability in this group. Onset is usually between 20 and 40 years of age. Patients with MS are thought to have an average life expectancy 7 years shorter than that of the general population, but this issue remains controversial 7. MS takes three main forms: RRMS: characterised by episodes of neurological dysfunction interspersed with periods of stability. Secondary progressive MS (SPMS): in which progressive neurological disability occurs later in the course of the disease. 2

3 Primary progressive MS (PPMS): in which progressive neurological disability occurs from the outset. An estimated 85,000 people in the UK have MS 8 with 2,500 newly diagnosed each year. RRMS is the most common form with approximately 40% of all MS cases (approximately 51,000 people) 9. Existing comparators and treatments Four general means of disease management target separately or in combination, different aspects of the disease. Management of symptoms and disability by speech-, physio- and occupational therapy, pharmacological or other therapeutic agents. Management of the emotional and social consequences of relapses and disability. Treatment of relapses with corticosteroids. Pharmacological action using disease modifying therapy (DMT) agents: o Interferon beta 1-a (Rebif, Avonex, and Betaferon) licensed for relapsing MS (not recommended by NICE, but available through the Department of Health risk sharing scheme). o Glatiramer (Copaxone), licensed for relapsing MS (not recommended by NICE, but available through the Department of Health risk sharing scheme). o Natalizumab (Tysabri) licensed for rapidly evolving severe MS or those patients in whom the other DMTs are no longer effective. Unlicensed immunosuppressants are sometimes used and include: methotrexate, cyclophosphamide, azothiaprine/cytoxan, mitoxantrone. Efficacy and safety Trial code NCT ; CLARITY; oral cladribine; RRMS; phase III 10. NCT ; ONWARD; add on oral cladribine with Rebif; phase II 11. Sponsor Merck Serono. Merck Serono. Status Ongoing Ongoing Location Switzerland USA Design Randomised, double-blind, placebo Randomised, double-blind, placebo Participants in trial controlled. n=1290; adults years; RRMS. During initial treatment in year 1 patients randomised to cladribine: 1. Low dose mg/kg/cycle for 2 cycles with placebo for 2 cycles. 2. High dose mg/kg/cycle for 4 cycles. 3. Placebo (4 cycles). During year 2, patients who have previously received high and low dose cladribine, receive cladribine 0.875mg/kg/cycle for 2 cycles. Patients on placebo continue with it in year 2. Patients who experience >1 relapse per year are offered interferon beta 1-a (Rebif) 44 µg 3 times a week. Follow-up 96 weeks 96 weeks Primary Safety and efficacy; relapse rate (RR). outcome controlled. n=260; adults; RRMS and SPMS; 48 weeks of interferon beta 1-a (Rebif) prior to screening. Randomised to cladribine: 1. Low dose mg/kg/cycle for 2 cycles with Rebif. 2. High dose mg/kg/cycle for 4 cycles with Rebif. 3. Placebo (4 cycles). During year 2, patients who have previously received high and low dose cladribine, receive cladribine 0.875mg/kg/cycle for 2 cycles. Patients on placebo previously continue on placebo (2 cycles), combined with Rebif (44 µg 3 time a week). Safety and efficacy; number of T1 gadolinium-enhanced lesions. 3

4 Secondary outcomes Expected reporting date Progression of disability; MRI outcomes. Study started January 2005; final analysis expected Q2-Q MRI parameters; disability. Study started December 2006; estimated completion: February Estimated cost and cost impact The cost of oral cladribine has not yet been determined. Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Services Increased use: may increase numbers assessed for treatment Decreased use: compared to sc options Reduced mortality or increased survival Service reorganisation required Improved quality of life for patients and/or carers None identified Staff or training required None identified Costs Increased unit cost compared to alternative New costs: may increase numbers receiving therapy References Increased costs: more patients coming for treatment Savings: Increased costs: capital investment needed 1 Langtry HD, Lamb HM. Cladribine: a review of its use in multiple sclerosis. Biodrugs. 1998; 9 (5): National Institute of Health and Clinical Excellence. Cannabinoids for the treatment of the symptoms of multiple sclerosis. Technology appraisal. Suspended (expected date of issue to be announced). 3 National Institute of Health and Clinical Excellence. Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis. Technology appraisal TA127.August 2007 (review date: June 2010). 4 National Institute of Clinical Excellence. Multiple sclerosis - beta interferon and glatiramer acetate. Technology appraisal TA32. January National Institute of Health and Clinical Excellence clinical guideline. Management of multiple sclerosis in primary and secondary care. Clinical guideline CG8. November Clinical Evidence. Multiple sclerosis. Available at: /nud/1202/1202_background.jsp (Accessed 17/3/08). 7 EMedicine. Multiple sclerosis. Available at: (Accessed 17/3/08). 8 Multiple Sclerosis Society. Multiple sclerosis. Available at: (Accessed 17/3/08). 9 MS Network online. Relapse remitting MS. Available at: /general/guide_understanding_ms/what_is_ms/how_does_ms_progress/relapsing_remitting_ms.jsp (Accessed 17/3/08). 10 Clinical Trial. Safety and efficacy of oral cladribine in subjects with relapsing-remitting MS. Available at: (Accessed 20/3/08). 11 Clinical Trial. Cladribine as an add-on to Rebif new formulation in MS subjects with active disease. Available at: (Accessed 20/3/08). 4

5 The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)