Mavenclad® (Cladribine) Tablets Approved by the FDA for Adults with Relapsing Forms of MS, Including Active SPMS

In a news release dated March 29, 2019, the United States Food and Drug Administration (FDA) announced the approval of Mavenclad® (cladribine) oral tablets to treat adults with relapsing forms of multiple sclerosis (MS). The approval is for individuals with relapsing-remitting MS (RRMS) and for individuals with active secondary-progressive MS (SPMS).

Mavenclad is not recommended for individuals with clinically isolated syndrome (CIS). According to the FDA, Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Because of its safety profile, it is not considered to be a first-line of treatment for MS.

Following the approval of Mayzent® (siponimod) oral tablets three days earlier, Mavenclad has become the second disease-modifying therapy (DMT) to be approved in recent years for active secondary-progressive MS. According to EMD Serono, the makers of Mavenclad, this medication “is the first and only FDA-approved treatment for RRMS and active SPMS that provides two years of proven efficacy with a maximum of 20 days of oral treatment, during a two-year period.” This medication will be available to patients within approximately two weeks of the approval date.

According to MSAA’s Chief Medical Consultant Dr. Jack Burks, “To have two treatments approved by the FDA within three days of one another is truly exciting. Additionally, both of these medications are not only indicated for people with relapsing-remitting MS, but also for individuals with active secondary-progressive MS, a patient population that previously had no realistic FDA-approved treatment options. What makes Mavenclad so unique is that it is an oral medication that is given in only two annual courses for a maximum of 20 days over a period of two years. No additional treatments are needed for the next two years, while treatments beyond the four-year time period have not yet been studied. We are greatly encouraged to see a second approved treatment for these two types of MS, giving individuals with MS more treatment options and more potential to receive the best possible medication for their specific disease course and situation.”

In clinical trials, cladribine has been shown to reduce disease activity in patients with relapsing MS, including disability progression, annualized relapse rate, and MRI activity. Potential adverse events include lymphopenia, a condition that causes abnormally low counts of white blood cells that play a role in fighting infection, and herpes zoster infection.

The FDA’s press release explains that most people with MS start with a relapsing-remitting course of symptom flare-ups and remissions, possibly with some degree of residual disability. Over time, some patients experience an increase in disability that is independent of relapses, and this is referred to as “secondary-progressive MS.” Initially, people with this form of MS may still experience relapses, which is referred to as “active” secondary-progressive MS – the form that Mavenclad is approved to treat. Without treatment, many of those with this form of MS eventually experience continued progression of disability without relapses, and this is referred to as “non-active” secondary-progressive MS. Mavenclad is not approved for this latter form of the disease.

This approval comes eight months after the announcement that the FDA had accepted a New Drug Application (NDA) for Mavenclad, previously referred to as “Cladribine Tablets.” At that time, this investigational treatment for relapsing forms of MS had already been accepted by the European Commission in August 2017 and by Canada in December 2017. It had also been approved for the treatment of relapsing MS in 38 countries under the trade name Mavenclad. Please see MSAA’s news item, “FDA Accepts Application for Cladribine Tablets,” for more information.

According to MSAA’s MS Research Update 2018, “Cladribine selectively targets the immune system’s B cells and T cells, leading to depletion of those cells. This is followed by a distinct pattern of ‘reconstitution,’ as new B cells and T cells are produced. The medication has an interesting dosing regimen, with two annual courses given for a maximum of 20 days over two years. Its developers note that this approach avoids continuous suppression of the immune system.” Following these first two years, no treatment is needed for Years 3 and 4.

The FDA’s approval of Mavenclad was based on the 96-week, Phase III CLARITY trial, where 1,326 patients with RRMS were randomized in a roughly 1:1:1 ratio to receive 3.5 mg of cladribine per kilogram (kg) of body weight, 5.25 mg/kg cladribine, or placebo. Either of the two doses, or the placebo, was given in two or four short courses for the first 48 weeks. This was followed by two short courses starting at Week 48 and Week 52, for a total of 8 to 20 days of treatment per year.

According to MSAA’s MS Research Update 2018, “Patients receiving cladribine at either dose had annualized relapse rates that were less than half the rate of individuals receiving placebo. Roughly 79 percent of the cladribine-treated patients did not have a relapse over the 96-week study period, as compared to 61 percent of people in the placebo group. Individuals receiving cladribine, at either dose, also had a lower risk of sustained progression of disability and a greater reduction in the number of brain lesions identified on MRI relative to the placebo group.”

The FDA explains that Mavenclad must be dispensed with a patient Medication Guide, describing important information about the drug’s uses and risks. Mavenclad has a Boxed Warning for an increased risk of malignancy (cancer) and fetal harm. Mavenclad is not to be used in patients who currently have or previously had a malignancy, nor should it be given to patients who have an increased risk of malignancy. Mavenclad should not be used in pregnant women, nor in women and men of reproductive potential who do not plan to use effective contraception during treatment and for six months after the course of therapy because of the potential for fetal harm. Mavenclad should be stopped if the patient becomes pregnant.

Other warnings include the risk of decreased lymphocyte (white blood cell) counts, and these should be monitored before, during, and after treatment. Mavenclad may increase the risk of infections, liver injury, and other health risks. Physicians need to screen for these conditions and stop treatment if necessary. The most common adverse reactions reported by patients receiving Mavenclad in the clinical trials include upper respiratory tract infections, headache, and decreased lymphocyte counts.  

EMD Serono’s patient assistance program, MS LifeLines, will offer personalized patient support for individuals who want to learn more about Mavenclad. These services include answers to medical questions as well as assistance with navigating insurance coverage questions and additional resources that may be able to assist eligible patients who are uninsured or underinsured. Please visit or call (877) 447-3243 for more information.

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to

Written by Susan Wells Courtney, MSAA Senior Writer

Reviewed by Dr. Jack Burks, MSAA Chief Medical Consultant