Multiple Sclerosis (MS)

Mavenclad (cladribine) is a disease-modifying drug by EMD Serono for multiple sclerosis (MS).1

The US Food and Drug Administration approved Mavenclad for the treatment of adult patients with relapsing forms of MS including relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS).2

The medicine is also authorized in the EU for the treatment of highly active relapsing MS. It has reduced relapse rates and delayed disease progression in patients with active forms of relapsing MS.3

Mavenclad comes in a 10 mg oral tablet form. The recommended dosage is 3.5 mg per kg body weight divided into 2 yearly treatment courses.4 It is only recommended for the treatment of patients who have not responded to or are unable to tolerate other disease-modifying MS treatments.2

Mavenclad’s Mechanism of Action

Mavenclad is a purine antimetabolite that impairs DNA synthesis, causing the depletion of B and T lymphocytes, which are involved in the pathogenesis of MS.5 It temporarily reduces the number of B and T lymphocytes, leading to a reduction in relapse rate and severity, as well as slowing down disability progression. However, the mechanism of action of Mavenclad in MS is not fully elucidated.

Because Mavenclad treatment does not suppress the immune system continuously, the risk of infections following treatment is lower compared to some other disease-modifying MS treatments. 

Warnings, Precautions, and Adverse Reactions

Mavenclad is easily destroyed in normal cells except for blood cells and, as a result, it causes relatively fewer side effects compared to other immunosuppressants as it does not target healthy cells.6 The concomitant use of Mavenclad with immunosuppressants or immunomodulatory or myelosuppressive drugs is not recommended as it increases the risk of adverse reaction due to additive effects.

However, treatment can still cause serious side effects, including low blood cell counts, liver problems, hypersensitivity, heart failure, some malignancies, and serious infections such as shingles (herpes zoster), tuberculosis, hepatitis B or C, and progressive multifocal leukoencephalopathy.1

Get detailed prescribing information on the Manvenclad monograph page on Rare Disease Advisor.

The most common side effects of Mavenclad are headaches, rash, hair thinning or alopecia, fever, abdominal pain, toothache, flu and flu-like symptoms, bronchitis or other chest infections, oral herpes, vaginal infections, diarrhea, nausea, vomiting, abdominal pain, back pain, and anxiety. Symptoms of gastroenteritis including diarrhea, vomiting, and abdominal pain are also among the side effects.6

Mavenclad may also cause birth defects and should not be used during pregnancy. Effective contraception must be used during the treatment course and for 6 months after the last dose of treatment. Mavenclad should also not be used while breastfeeding.1

Mavenclad is contraindicated in patients with cancer, those who are HIV positive, or those who have active infections including tuberculosis and hepatitis B or C.1

Efficacy in Clinical Trials

The safety and efficacy of Mavenclad have been tested in one main phase 3 clinical trial titled CLARITY.7 The randomized, double-blind, 3-arm, placebo-controlled, multicenter trial enrolled 1326 participants aged 18 to 65 years with RRMS who had at least 1 relapse within the last year but no relapse within the 28 days before the trial and had an Expanded Disability Status Scale (EDSS) score between 0 and 5.5.

Participants were assigned in a 1:1:1 ratio to either 3.5 mg per kg of body weight or 5.25 mg per kg of body weight of cladribine or a placebo.

The primary endpoint of the study was the annualized qualifying relapse rate. Secondary outcome measures included the percentage of relapse-free participants, the time to disability progression, and the mean number of combined unique lesions, active T2 lesions, and active T1 gadolinium-enhanced (Gd+) lesions on magnetic resonance imaging (MRI).

The results of the study showed that patients who were treated with either dose of cladribine had significantly lower annualized relapse rates compared to those who received the placebo.8 The relapse-free rate was also higher in patients treated with cladribine. Finally, those treated with cladribine had a lower risk of 3-month sustained progression of disability and significant reductions in brain lesion count on MRI.

Further analysis of data from the trial showed that the annualized percentage of brain volume change was reduced in patients treated with either dose of cladribine compared to those who received the placebo.9 There was a significant correlation between the annualized percentage of brain volume change and the cumulative probability of disability progression; patients with a lower annualized percentage of brain volume change had the highest probability of remaining free from disability progression at 2 years. It also showed reduced brain atrophy for patients who took cladribine compared to placebo.

To assess the effect of cladribine treatment on health-related quality of life factors in people with RRMS, information about the patients who took part in CLARITY was obtained from the European Medicines Agency. The analysis of the data showed that patients taking either dose of cladribine had significantly improved on the Euro Quality of Life 5 Dimensions (EQ-5D) index scores after 2 years compared to those who received the placebo.10 There were also positive differences in the Multiple Sclerosis Quality of Life-54 (MSQOL-54) scores between the cladribine and placebo treatment groups. However, these differences were not statistically significant.


  1. Mavenclad® (cladribine) tablets 10 mg. EMD Serono. Updated November 2020. Accessed June 15, 2021.
  2. Mavenclad. National Multiple Sclerosis Society. Accessed June 15, 2021.
  3. Mavenclad: cladribine. European Medicines Agency. September 8, 2017. Accessed June 15, 2021.
  4. Mavenclad dosage. Updated March 31, 2021. Accessed June 15, 2021.
  5. Ostrovsky L. Mavenclad (cladribine) first short-course oral therapy approved for relapsing-remitting multiple sclerosis and active secondary progressive disease. American Health & Drug Benefits. Accessed June 15, 2021.
  6. Mavenclad. MS Society of Canada. Accessed June 15, 2021. 
  7. A safety and efficacy study of oral cladribine in subjects with relapsing-remitting multiple sclerosis (RRMS) (CLARITY). September 21, 2005. Updated February 7, 2014. Accessed June 15, 2021.
  8. Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416-426. doi:10.1056/NEJMoa0902533
  9. De Stefano N, Giorgio A, Battaglini M, et al. Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets. Mult Scler. 2018;24(2):222-226. doi:10.1177/1352458517690269
  10. Afolabi D, Albor C, Zalewski L, Altmann DR, Baker D, Schmierer K. Positive impact of cladribine on quality of life in people with relapsing multiple sclerosis. Mult Scler. 2018;24(11):1461-1468. doi:10.1177/1352458517726380

Reviewed by Debjyoti Talukdar, MD, on 7/1/2021.