Mavenclad (cladribine) for multiple sclerosis
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What is Mavenclad for MS?
Mavenclad (cladribine) is a short-course oral treatment for people with relapsing multiple sclerosis (MS) that works to reduce disease exacerbations and delay the progression of disability. It also reduces the number of brain lesions visible on MRI scans.
The therapy is sold by EMD Serono (known as Merck KGaA outside the U.S. and Canada).
Therapy Snapshot
| Brand name: | Mavenclad |
| Chemical name: | Cladribine |
| Usage: | Disease-modifying therapy for RRMS and active SPMS |
| Administration: | Oral tablets |
How does Mavenclad work?
In MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers. Damage to myelin disrupts nerve signals from being effectively transmitted and can lead to permanent nerve cell damage.
Mavenclad works by reducing the number of certain immune cells circulating in the bloodstream. It particularly targets immune B-cells and T-cells, the main drivers of inflammation and new brain lesions in MS.
The active ingredient in Mavenclad, cladribine, has a similar chemical structure to purine — one of the building blocks of DNA — and gets incorporated into the genetic material of these immune cells. This interferes with DNA repair and replication and leads to immune cell death, reducing the damaging immune responses in those with MS.
A formulation of cladribine that is infused intravenously, or into the bloodstream, is approved to treat certain leukemias and lymphomas caused by an excessive proliferation of B-cells or T-cells.
Who can take Mavenclad?
The U.S. Food and Drug Administration approved Mavenclad in 2019 for the treatment of adults with relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).
Because of its safety profile, Mavenclad is generally recommended in the U.S. for patients who do not tolerate or have failed to respond to other MS treatments.
In the European Union, Mavenclad was approved in 2017. It is indicated for adults with highly active relapsing MS, as defined by certain clinical or imaging features.
According to Merck KGaA, Mavenclad has been approved in more than 80 countries. However, in some of them, such as Canada and Australia, the medication is solely approved to treat RRMS.
Who should not take Mavenclad?
Due to its safety profile, Mavenclad is not recommended for use in people with clinically isolated syndrome (CIS) — those who have experienced a first episode of MS-like neurological symptoms but are not diagnosed with overt MS.
The medication also should not be taken by anyone who:
- currently has cancer.
- is pregnant.
- is of childbearing age of either sex and not planning to use effective contraception during treatment and for at least six months after the last dose.
- plans to breastfeed while on Mavenclad.
- has a human immunodeficiency virus (HIV) infection.
- has active chronic infections, such as hepatitis or tuberculosis.
- has experienced an allergic reaction to cladribine or to any other component in Mavenclad.
How is Mavenclad administered?
Mavenclad is available in 10 mg tablets, taken orally. It is administered in two courses of treatment over two years. Each course consists of two treatment cycles of about two weeks each, generally spaced about one month apart, at the beginning of each treatment year.
The total treatment dose is 3.5 mg per kilogram of body weight. In each treatment course, patients receive a dose of 1.75 mg/kg, which is given in two cycles of one or two daily tablets taken over four or five consecutive days.
The total number of tablets per cycle varies based on a person’s weight. Someone weighing from 60–70 kg (132–154 pounds) would take a total of six tablets in each cycle. Another person weighing 100–110 kg (220–242 pounds) would receive 10 tablets per treatment cycle.
Mavenclad should be swallowed whole without chewing and can be taken with and without food. Patients should not take more than two tablets per day.
| Administration | Oral tablets |
| Dosage | Total treatment dose of 3.5 mg per kilogram of body weight |
| Timing | Administered in two courses of treatment over two years (two treatment cycles of about two weeks each, generally spaced about one month apart, at the beginning of each treatment year) |
Mavenclad in clinical trials
Mavenclad’s approval was supported by data from multiple studies, including three Phase 3 clinical trials — CLARITY (NCT00213135), CLARITY extension (NCT00641537), and ORACLE-MS (NCT00725985), all of which demonstrated the therapy’s effectiveness.
CLARITY and CLARITY extension trials
CLARITY enrolled 1,326 adults with RRMS and compared the effects of two doses of Mavenclad — 3.5 or 5.25 mg/kg — with a placebo over 96 weeks, or just under two years. Results showed that the 3.5 mg/kg dose reduced relapse rates by 58% compared with the placebo. It also lowered the number of brain lesions by more than 70% relative to the placebo. The lower dose also reduced the risk of three-month confirmed disability progression by 33%.
In the CLARITY extension, a total of 867 participants who completed the initial trial were again randomly assigned to two more years of Mavenclad (3.5 mg/kg) or a placebo. Findings showed the treatment continued to limit relapses two years after it was last administered, regardless of patients receiving Mavenclad or a placebo in the extension trial. In the group of patients who received the approved dose of Mavenclad, nearly 75% were free of relapses four years after starting treatment.
ORACLE-MS trial
The ORACLE-MS trial investigated whether Mavenclad could delay or prevent progression to clinically definitive MS in 616 patients with CIS. Participants were randomly assigned to receive Mavenclad (at 5.25 or 3.5 mg/kg doses), or a placebo, for 96 weeks. Compared with a placebo, the 3.5 mg/kg dose of Mavenclad significantly lowered the risk of progression to clinically definitive MS by 50%. The treatment also reduced the appearance of new brain lesions on MRI scans by nearly 80%.
CLARIFY-MS and CLASSIC-MS trials
EMD Serono also conducted several Phase 4 clinical trials — those done post-approval in a real-world setting. CLARIFY-MS (NCT03369665) enrolled 482 people with highly active relapsing MS, all of whom were treated with the approved dose of Mavenclad. Treatment with Mavenclad improved quality of life for these individuals, the results indicated.
Another Phase 4 study called CLASSIC-MS (NCT03961204) included patients from previous Mavenclad Phase 3 clinical trials and followed them for up to 15 years. A median of 10.9 years after their last dose, significantly fewer patients who received Mavenclad than placebo had progressed to the point where they required a wheelchair (77.8% vs. 90%) or walking aids (75.6% vs. 81.2%). Patients who received the therapy also were less likely to require further treatments.
Ongoing trials
A Phase 2 trial called ChariotMS (NCT04695080) is now investigating Mavenclad in adults with progressive forms of MS. Eligible participants cannot walk with two crutches for more than 20 meters (about 65 feet) or are unable to walk at all, but still have some use of their arms and hands. The study aims to enroll up to 200 patients at 20 sites in the U.K. The goal of the trial is to determine if Mavenclad can slow hand and arm function decline. ChariotMS is expected to be completed in 2024.
Common side effects of Mavenclad
The most common side effects of Mavenclad, as seen in MS clinical trials, are:
- headache
- low levels of lymphocytes, a type of immune cell
- upper respiratory tract infection
Other concerns regarding the use of this therapy that may have more severe consequences include a possible increased risk of infections due to immune system suppression or liver problems. The therapy also carries an additional warning for cancer patients.
Low blood cell counts
Mavenclad treatment often results in atypically low counts of lymphocytes, a class of immune cells that includes B-cells and T-cells. It also may cause abnormally low levels of other components in the blood, such as neutrophils, platelets, and hemoglobin. Blood and immune cell counts should be monitored before, and regularly during, treatment with Mavenclad.
Infections and vaccines
Because it reduces the activity of the immune system, Mavenclad may increase the risk of infections. Preventive measures to lower infection risks — such as vaccinations against the virus varicella zoster, which causes chickenpox and shingles, or prophylactic treatment with anti-herpes therapies — are recommended for patients on Mavenclad.
Vaccines that contain a living virus should not be given to individuals who have been treated with Mavenclad until their immune cell counts return to normal ranges.
Blood transfusion reactions
Patients on Mavenclad who receive a blood transfusion may in rare cases experience transfusion-associated graft-versus-host disease. This is a condition in which immune cells in the transfused blood start to attack healthy tissue in the recipient’s body. To reduce this risk, it is recommended that cellular blood components be irradiated to kill immune cells prior to infusion.
Cancer
Mavenclad carries a boxed warning that it can increase cancer risk. It should not be given to patients with cancer, and the benefits and risks of therapy should be carefully weighed in the event that a high cancer risk is already known.
Liver injury and heart failure
In very rare cases, Mavenclad-treated MS patients may experience serious liver injury. Liver health should be monitored prior to the first and second treatment courses. If patients show signs of substantial liver injury, Mavenclad treatment should be paused or stopped, as appropriate.
In clinical trials, one MS patient given Mavenclad experienced a life-threatening event of heart failure. Similar rare reactions also have occurred with other formulations of cladribine in other indications. Patients who experience signs of heart failure — such as shortness of breath, rapid or irregular heartbeat, or swelling — should seek immediate medical attention.
Allergic reactions
Allergic reactions to Mavenclad, including serious reactions, have been reported. Treatment with this medication should be stopped if an allergic reaction is suspected.
Pregnancy and breastfeeding
Mavenclad can cause injury to a developing fetus. It also may cause abnormalities in sperm or egg cells that increase the risk of harm if a child is conceived from those cells. As such, Mavenclad should only be used to treat people with reproductive potential if they are consistently using contraceptive methods to avoid pregnancy for at least six months after each course of treatment. Female patients able to become pregnant may be advised to use additional birth control during the Mavenclad treatment cycle
Breastfeeding also is not recommended until at least 10 days after the most recent dose because the therapy can pose risks to infants.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Mavenclad
The U.S. Food and Drug Administration (FDA) approved Mavenclad in March 2019 to treat relapsing forms of multiple sclerosis, namely relapsing-remitting multiple sclerosis and active secondary progressive multiple sclerosis.
Because it interferes with DNA replication, Mavenclad may cause damage to a developing fetus. Patients who have the potential to become pregnant or father a child are recommended to use effective contraception for at least six months after their last dose in each treatment course.
Mavenclad is not known to interact with alcohol. However, certain adverse reactions such as headache or liver damage may be more likely if patients consume alcohol while taking Mavenclad, given that both drugs can cause these effects individually. Patients are advised to talk to their healthcare teams about safe alcohol consumption.
Benefits may be seen in some patients in as little as 3.5 months. In the ORACLE-MS trial, which compared Mavenclad with a placebo in more than 600 patients with clinically isolated syndrome, a significant reduction in brain lesions was evident with Mavenclad as soon as 13 weeks. However, as each individual may respond differently to the medication, the benefits of Mavenclad for each particular patient should be discussed with a person’s healthcare team.
Weight gain has not been reported as a side effect of Mavenclad in clinical trials, but some people who received the medication in the CLARITY trial did experience hair loss. Individuals who experience unanticipated effects after starting treatment are advised to talk about such issues with their healthcare providers.
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