Drug Identification Number (DIN): 02470179
EMD Serono, a Division of EMD Serono Canada Inc.
MAVENCLAD™, also known as cladribine, is an oral selective Immunosuppressant. It is indicated as monotherapy for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical exacerbations and delay the progression of disability. MAVENCLAD™ is generally recommended in individuals who have had an inadequate response to, or are unable to tolerate, one or more therapies for multiple sclerosis. In large clinical trials MAVENCLAD™ was shown to decrease the number of MS relapses that occur and helped to slow the accumulation of physical disability caused by MS.
Indications and use
MAVENCLAD™ is indicated as monotherapy for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical exacerbations and delay the progression of disability. MAVENCLAD™ is generally recommended in MS patients who have had an inadequate response to, or are unable to tolerate, one or more therapies for multiple sclerosis.
MAVENCLAD™ treatment should be initiated and supervised by neurologists experienced in the treatment of MS and who have fully familiarized themselves with the efficacy and safety profile of MAVENCLAD™ and are able to discuss benefits/risks with patients.
Administration and dose
MAVENCLAD™ is taken as two treatment courses over 2 years. Each treatment course consists of 2 treatment weeks, which are one month apart at the beginning of each treatment year. A treatment week consists of 4 or 5 days of taking one or two, 10mg tablets orally, with or without food, daily. After the second dose in year two of treatment, individuals are observed for an additional two years. The recommended cumulative dose of MAVENCLAD™ is 3.5 mg/kg body weight over 2 years (1.75 mg/kg per year).
Mechanism of action (MOA)
Although the exact mechanism of action is not fully understood, it is thought that MAVENCLAD™ selectively targets and accumulates in certain types of white blood cells (lymphocytes), such as disease-causing T cells. MAVENCLAD™ predominantly and temporarily reduces B & T lymphocytes followed by a natural re-building of lymphocytes, without continuous suppression of the immune system. By interfering with a target cell’s ability to process DNA, it leads to the depletion of disease-causing lymphocytes and results in reduced inflammation. MAVENCLAD™ is easily destroyed in normal cells except for blood cells, resulting in relatively few side effects as the drug does not target other, healthy cells.
Common side effects: nausea, headache, cold sores (oral herpes), rash, thinning or hair loss, fever, abdominal pain, toothache, flu and flu like symptoms, cold symptoms, bronchitis or other chest infections, symptoms of gastroenteritis (diarrhea, vomiting, abdominal pain), back pain, anxiety, vaginal infection.
More serious side effects: reduction in the number of certain white blood cells, shingles and rare serious side effects may include, tuberculosis, with symptoms such as cough that does not go away, fever or loss of weight.
This is not a comprehensive list of all possible side effects of MAVENCLAD™. Please see the MAVENCLAD™ Product Monograph for a list of other potentially serious side effects. It is important that those with MS discuss side effects about any medication they are considering with their physician. (*Health Canada, product monograph for MAVENCLAD™.)
A phase III clinical trial (CLARITY) tested the safety and efficacy of oral cladribine in 1,326 participants living with relapsing remitting MS. The randomized, double-blind trial compared the effects of two doses of cladribine (3.5 mg/kg, and 5.25 mg/kg) against a dummy treatment (placebo) and followed the participants for up to 2 years. Treatment with cladribine caused a 58% reduction in annual relapse rate compared to placebo at the lower dose and 55% at the higher dose. Participants taking cladribine also had a lower risk of sustained disability progression at 3 months and had fewer brain lesions as seen on imaging scans.
CLARITY extension study: a two-year Phase III placebo-controlled study following on from the CLARITY study. In this extension study, 806 patients received either placebo or a cumulative dose of cladribine 3.5 mg/kg (in a regimen similar to that used in CLARITY) over a 96-week study period. The primary objective of this study was safety, while efficacy endpoints were exploratory. The safety outcomes were consistent with the safety profile observed for the previous CLARITY study.
MAVENCLAD™ is currently being evaluated by the Canadian Agency of Drugs and Technologies in Health (Common Drug Review) who will provide a recommendation for provincial public plan coverage for all Canadian provinces except Quebec. The Institut national d’excellence en sante et en services sociaux (INESSS) in Quebec conducts an independent review.
Drug support program
1. Giovannoni G et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. NEJM 2010;362(5):416-26.
2. Hartung HP, et al. Development of oral cladribine for the treatment of multiple sclerosis. J Neurol. 2010;257(2):163-170.
3. Pakpoor J, et al. No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine. Neurol Neuroimmunol Neuroinflamm. 2015;2:e158.
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