Mavenclad (cladribine), an anti-cancer therapy, has been developed by EMD Serono (Merck KGaA outside of the U.S. and Canada) as a disease-modifying and short-course oral treatment for people with active and relapsing forms multiple sclerosis (MS).
Mavenclad is now approved to treat relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (SPMS) by the U.S. Food and Drug Administration (FDA). It is also approved in a number of other countries, but not all regulatory agencies favor a broad definition of relapsing disease that might include patients with a progressive form.
The treatment is typically recommended for patients who failed to respond to, or were unable to tolerate, other MS therapies.
How Mavenclad works
In MS the immune system mistakenly attacks the myelin sheath, a protective protein layer that surrounds nerve fibers. Damage to the myelin sheath disrupts the effective transmission of nerve signals and can lead to permanent damage to nerve cells.
Mavenclad works by reducing the number of immune cells, called B-cells and T-cells, that are circulating in the bloodstream. Cladribine (the active ingredient in Mavenclad) interferes with DNA repair and replication, which leads to cell death. This results in fewer immune cells available and reduces the damaging immune response seen in MS.
It is a short-course therapy in that it is given in two courses of oral treatment over two years, with two treatment weeks (generally spaced one month apart) at the beginning of each treatment year.
Mavenclad in clinical trials
Mavenclad has gone through several rounds of testing for RRMS. The results of a Phase 3 clinical trial (NCT00213135) called CLARITY, which involved more than 1,300 adult patients with RRMS, 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 kg of body weight) with a placebo. Both doses reduced patient 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 (NCT00725985) called ORACLE included 617 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 pain, fatigue, loss of vision, and bladder or bowel problems). The trial also showed that for patients who took Mavenclad tablets after a first demyelinating event, the risk of the disease progressing to MS itself was significantly reduced, compared with those who took placebo. Those who received Mavenclad during the initial treatment phase of the clinical trial showed lower annualized relapse rates than those who received a placebo during initial treatment.
MS patients who participated in Mavenclad studies can have their names added to a register (NCT01013350), which will be used to continue to assess the safety of the treatment.
A Phase 4 clinical trial (NCT03364036) to determine when Mavenclad first begins to work (show action), using magnetic resonance imaging (MRI) in patients with highly active relapsing MS, is currently recruiting an estimated 300 adults in Australia, Canada, Europe, Israel, and the U.K. During this two-year study, participants will receive 1.75 mg per kg of body weight of Mavenclad in one treatment per year. Lesion size (a measure of MS severity) will be assessed at the study’s beginning, and six months after. Immune cell numbers will be assessed from blood samples taken every three months throughout the trial.
Another Phase 4 clinical trial (NCT03369665) is recruiting an estimated 445 adult patients with highly active relapsing MS at 23 sites in the EU to assess quality of life over the course of two years. Patients will receive 1.75 mg per kg of body weight of Mavenclad in one treatment each year. The multiple sclerosis quality of life-54 questionnaire will be used to assess quality of life at the beginning and end of the study.
Based on positive results from the clinical trials, Merck applied to the European Medicines Agency (EMA) for the approval of Mavenclad as a treatment for RRMS in July 2016. The European Commission approved Mavenclad on Aug. 25, 2017, to be used in the 28 countries of the E.U. as well as in Norway, Liechtenstein, and Iceland. Health authorities in Canada approved the treatment on Dec. 6, 2017, and the FDA announced its decision on March 29, 2019.
Side effects of Mavenclad treatment include headaches, common cold symptoms, and lymphocytopenia or low white blood cell counts, which can increase the risk of infections, including that of the herpes virus (shingles or cold sores).
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