Mavenclad (cladribine) is an anti-cancer drug being developed by Merck as a possible treatment for relapsing-remitting multiple sclerosis (RRMS). The oral therapy works by selectively targeting lymphocytes, immune cells believed to be linked to multiple sclerosis.

How Mavenclad works

MS symptoms are a result of the body’s immune system mistakenly attacking the myelin sheath, a protective layer that surrounds nerve fibers. Damage to myelin disrupts the effective transmission of nerve signals and can lead to permanent damage to the nerves.

The immune system can damage myelin by directing immune cells (white blood cells or lymphocytes), called T- and B-cells, in the brain and spinal cord to attack the myelin sheath.

Mavenclad works by reducing the number of B-cells and T-cells that are circulating in the bloodstream. It can interfere with DNA repair and replication in T- and B-cells, leading to cell death. This results in fewer cells available to cause the damaging immune response.

Mavenclad in clinical trials

Mavenclad has gone through several rounds of testing for RRMS. The results of a Phase 3 clinical trial, called CLARITY (NCT00213135) and involving more than 1,300 RRMS patients, were published in the New England Journal of Medicine. The study compared the effects of two doses of Mavenclad (3.5 mg or 5.25 mg per kilogram) with a placebo. Both doses reduced patients’ relapse rate by more than 50 percent. Results from an extension study (NCT00641537) showed that Mavenclad continued to limit relapses two years after it was administered.

Another Phase 3 clinical trial called ORACLE (NCT00725985) included 616 participants. It showed that taking Mavenclad after an initial demyelinating event delayed the onset of MS. (A demyelinating event is a show of symptoms resulting from the deterioration of the myelin sheath. Initial demyelination-event symptoms include nerve pain, fatigue, loss of vision, and bladder or bowel problems). The trial also showed that in people who took Mavenclad tablets after a first demyelinating event, the risk of the disease progressing to MS itself was significantly reduced, compared to those who took placebo. Those who received Mavenclad during the clinical trial’s initial treatment phase ended up with lower annualized relapse rates than those who received a placebo during initial treatment.

MS patients who have participated in Mavenclad studies can have their names added to a register (NCT01013350) dealing with the drug’s safety until late 2018.

Based on these positive results, Merck applied to the European Medicines Agency (EMA) for Mavenclad’s approval as a treatment for RRMS in July 2016. On August 25, 2017, the European Commission (EC) approved Mavenclad in the 28 countries of the European Union in addition to Norway, Liechtenstein, and Iceland.

Merck also announced that it is considering filing a new request for approval to the U.S. Food and Drug Administration (FDA), which rejected a similar request in 2011 (as did the EMA in 2010). Both those rejections were based on concerns of more cancer cases among Mavenclad-treated patients, but extension trials have since proven the treatment’s safety and efficacy.

Side effects of Mavenclad treatment include headaches, symptoms of the common cold, and lymphocytopenia or low white blood cell counts, a possible cause of infections.
