Kesimpta (ofatumumab) for multiple sclerosis

Last updated Feb. 28, 2025, by Patricia Silva, PhD
Fact-checked by Ines Martins, PhD

What is Kesimpta for MS?

Kesimpta (ofatumumab) is an anti-CD20 antibody approved for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).

Administered via monthly subcutaneous (under-the-skin) injections, it is used to prevent relapses, reduce MRI lesions, and slow disability progression.

Kesimpta was first developed by the Danish biotechnology company Genmab, but Novartis acquired the rights to the medication in 2015.

Therapy Snapshot

How does Kesimpta work for MS?

MS is an autoimmune disease in which the body’s immune system mistakenly attacks and damages the myelin sheath, a fatty layer that insulates and protects nerve fibers. Many types of immune cells are believed to drive this immune attack. Those include B-cells, the cells responsible for making antibodies.

Kesimpta is a monoclonal antibody that targets the CD20 protein. The medication triggers the death of the inflammation-driving B-cells via two main mechanisms: antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

In ADCC, the binding of the antibody to its target signals other immune cells to destroy the B-cell. In CDC, the antibody activates the complement cascade, a group of immunological proteins that directly kill the target cell. Kesimpta is thought to exert its effects mainly through CDC.

Because it is delivered via a subcutaneous injection, Kesimpta more effectively targets B-cells in lymph nodes, which are specialized immune structures where disease-causing B-cells can activate other immune cells to attack the brain and spinal cord. By eliminating these B-cells, Kesimpta is thought to reduce nerve cell damage and slow the progression of MS.

Kesimpta spares certain B-cells that are important for maintaining a healthy immune function.

Who can take Kesimpta?

Kesimpta was approved by the U.S. Food and Drug Administration in August 2020 for adults with relapsing forms of MS, including CIS, RRMS, and active SPMS.

In March 2021, the medication was approved in Europe, where it is indicated for adults with relapsing forms of MS and active disease, as defined by certain clinical or imaging features. Kesimpta also is approved in Canada and Australia, among other countries.

Who should not take Kesimpta?

Kesimpta is contraindicated, or not recommended, for people with:

• an active infection with the hepatitis B virus (HBV). Patients should be screened for HBV before starting on the medication.
• a history of an allergic reaction to ofatumumab, the active ingredient in Kesimpta. These may include a serious allergic reaction called anaphylaxis and swelling.
• a previous life-threatening, injection-related reaction to the medication.

How is Kesimpta administered?

Kesimpta is given via subcutaneous injections. After the first injection, which should be administered with guidance from a healthcare professional, the medication can be self-administered by patients at home or on the go.

The medication is available as a clear to slightly brownish-yellow solution and comes in two forms:

• a single-dose prefilled syringe
• an autoinjector pen called the Sensoready Pen.

Kesimpta is given at a recommended dose of 20 mg. When starting the medication, patients will receive three starter doses, one per week for the first three weeks. They should then skip one week and initiate once-monthly treatment on the fifth week.

Kesimpta should be administered in the abdomen, thigh, or outer upper arm. It should not be injected into moles, scars, stretch marks, or regions where the skin is tender, bruised, or hard.

The injection usually takes less than a minute, about 3-4 seconds if the auto-injector pen is used. No premedications are needed before receiving Kesimpta, and no post-dose observation is required.

About 15 to 30 minutes before administration, Kesimpta’s pen or syringe should be taken from the refrigerator and allowed to reach room temperature. Kesimpta’s pens/syringes are designed for one-time use only. Additional instructions for administering Kesimpta are available.

Kesimpta in clinical trials

The approval of Kesimpta in the U.S. was largely based on data from two identical Phase 3 clinical trials, ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231), that collectively enrolled more than 1,800 patients with RRMS or active SPMS at nearly 400 sites worldwide.

ASCLEPIOS trials

Participants in the ASCLEPIOS trials were randomly assigned to receive 20 mg Kesimpta or Aubagio (teriflunomide), an approved oral MS treatment, for up to 30 months (2.5 years). Kesimpta was given as three weekly subcutaneous injections, followed by every-four-week dosing.

The main goal of both studies was to determine if Kesimpta could significantly reduce the average number or relapses per year, known as the annualized relapse rate, compared with Aubagio. That goal was met, with Kesimpta resulting in a 51% reduction in relapse rates in ASCLEPIOS I and a 58% reduction in ASCLEPIOS II.

The risk of confirmed disability worsening, defined as a sustained increase in Expanded Disability Status Scale (EDSS) scores, was also significantly reduced with Kesimpta. Disability worsening lasting three months or more was observed in 10.9% of patients on Kesimpta compared with 15% of those on Aubagio — a 34% risk reduction — while the rates of disability worsening lasting at least six months were 8.1% for Kesimpta and 12% for Aubagio, a 32% reduction.

Disability improvement, or a reduction in EDSS scores confirmed at a subsequent appointment at least six months later, was also 35% more likely to occur in the Kesimpta group.

Kesimpta also significantly outperformed Aubagio in reducing the number of lesions with active inflammation by more than 90%, and new or enlarging lesions were reduced by more than 80%.

ALITHIOS extension trial

Participants who completed the ASCLEPIOS trials and other Kesimpta trials were given the option to enroll into an Phase 3 open-label extension study (NCT03650114), in which all are being treated with Kesimpta for up to eight years.

Due to be completed in 2028, this extension trial is following about 90% of the ASCLEPIOS participants and is also recruiting patients at various locations around the world.

After as long as five years of treatment in the ASCLEPIOS and ALITHIOS trials, participants initially assigned to Kesimpta had low relapse rates — fewer than 0.05 relapses per year — and their MRI disease activity was profoundly suppressed. The proportion of patients with no evidence of disease activity (NEDA-3), which refers to no new relapses, no signs of disease activity on MRI scans, and no confirmed disability worsening, also increased over time in the continuous Kesimpta group: At year five, 93.4% of patients achieved NEDA-3.

Those who started on a placebo and switched to Kesimpta in the extension trial also experienced pronounced reductions in their relapse rates and MRI lesions, and their NEDA-3 rates increased after switching as well.

Common side effects of Kesimpta

The most common side effects associated with Kesimpta are:

• upper respiratory tract infection
• headache
• injection-related reactions
• local injection site reactions.

Low antibody levels and infections

Kesimpta can decrease levels of infection-fighting antibodies, and this may increase the risk of infections. Antibody levels should be measured before starting on Kesimpta, and also routinely during treatment in certain patients. If patients have recurrent or opportunistic infections, or if prolonged antibody depletion requires treatment, the individual’s healthcare team may consider permanently stopping Kesimpta.

In clinical trials, the most common infections experienced during treatment with Kesimpta were in the respiratory and urinary tracts. While no MS patients on Kesimpta experienced a reactivation of the HBV virus, this has been reported in people who received ofatumumab, the active ingredient in Kesimpta, for another indication. In some patients, HBV reactivation resulted in severe liver inflammation, liver failure, and death.

Progressive multifocal leukoencephalopathy (PML), a rare and serious brain infection, has not been reported in MS patients using Kesimpta, but has developed in other patients given ofatumumab. This infection has also been observed in individuals treated with other anti-CD20 antibodies. If signs of PML appear, the patient should be promptly evaluated, and treatment should be permanently discontinued if the infection is confirmed.

Kesimpta also should be delayed in patients with an active infection.

Vaccines

Vaccination with live or live-attenuated viruses is not recommended during treatment with Kesimpta, and it’s not known if the medication can interfere with the effectiveness of non-live vaccines. For that reason, all vaccines should be given according to recommendations at least 2-4 weeks before starting Kesimpta.

Because Kesimpta can reduce B-cell levels in babies exposed to the medication before birth, these babies also should not receive live or live-attenuated vaccines until their B-cell levels return to normal. Non-live vaccines may be administered, but an assessment to determine if an effective immune response was mounted should be considered.

Injection-related and allergic reactions

Treatment with Kesimpta may result in injection reactions that cause symptoms affecting the whole body, including fever, headache, muscle pain, chills, and fatigue. These reactions most commonly occurred within 24 hours of the first injection, but were also observed with later injections.

Symptoms of an injection reaction may sometimes be indistinguishable from acute allergic reactions to the medications. For that reason, patients should receive the first injection under the guidance of a healthcare professional with appropriate training. If new or more severe symptoms appear in the following reactions, these may be from a potential allergic reaction.

If an infusion reaction occurs, the following injection should be administered under clinical observation. If that reaction is life-threatening, or if an allergic reaction of any severity occurs, treatment should be immediately and permanently discontinued.

Use in pregnancy and breastfeeding

According to animal data, Kesimpta may cause harm to a developing fetus. There’s also data showing that CD20 inhibitors such as Kesimpta can cause a temporary reduction in B-cell and other white blood cells in infants exposed to these medications during pregnancy. Patients with the capacity to become pregnant are advised to use contraception while on Kesimpta and for six months after stopping the therapy.

It is not clear if Kesimpta can pass into breast milk, or if it can have a negative effect on the nursing infant, so patients who are breastfeeding or plan to breastfeed while taking Kesimpta should inform their healthcare providers.

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.