Kesimpta (Ofatumumab) for Multiple Sclerosis

Kesimpta (ofatumumab) is an anti-CD20 antibody that has been shown to reduce relapse rates and the risk of disability progression for people with multiple sclerosis (MS).

The Danish biotechnology company Genmab first developed the treatment and licensed it to GlaxoSmithKline. Novartis acquired the rights to the medication in 2015.

Therapy Snapshot

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

Kesimpta is an antibody that targets the CD20 protein, which is found on the surface of most B-cells. By binding to CD20, Kesimpta can ultimately kill these inflammation-driving B-cells, which is thought to prevent further nerve cell damage and slow disease progression.

The U.S. Food and Drug Administration approved Kesimpta in 2020 for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).

The European Commission approved Kesimpta the following year to treat relapsing MS in adults with active disease. Kesimpta also is approved in Canada, Australia, Japan, and Switzerland, among other countries.

People with active hepatitis B virus (HBV) infection should not take Kesimpta. Patients should be screened for HBV before starting on the medication.

Kesimpta is given via a subcutaneous, or under-the-skin, injection at a dosage of 20 mg.

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

In the U.S., Canada, U.K., EU, and many other countries where Kesimpta is approved for MS, the medication is authorized for at-home administration, though the first injection should be performed under the guidance of a healthcare professional.

Kesimpta should be administered in the abdomen, thigh, or outer upper arm. 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.

Preclinical studies in animal models produced promising results that helped the developers proceed to Phase 1 clinical trials, in which the safety of Kesimpta was tested among healthy volunteers. With positive safety and toxicity findings from these trials, the therapy was moved forward to Phase 2 and 3 trials.

A pilot Phase 2 trial (NCT00640328) that enrolled 38 RRMS patients tested different doses of Kesimpta, or a placebo, for 24 weeks (about six months), after which participants switched to the opposite treatment for another six months. The therapy was given through intravenous (into-the-vein) infusions every two weeks.

Trial results showed a significant reduction in the number of brain lesions — areas of damage visible on MRI scans.

MIRROR trial

A larger placebo-controlled Phase 2 trial, called MIRROR (NCT01457924), then enrolled 232 people with RRMS to confirm the initial findings. Participants were randomly assigned to receive a placebo or one of four subcutaneous Kesimpta dosing regimens — 3 mg, 30 mg, or 60 mg of Kesimpta every 12 weeks, or 60 mg of Kesimpta every four weeks — for 24 weeks, or about six months.

Results of the MIRROR trial showed that treatment with Kesimpta rapidly depleted B-cells and effectively reduced the formation of new brain lesions compared with a placebo.

ASCLEPIOS trials

Kesimpta’s approval was based on data from two identical Phase 3 clinical trials, ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231), each enrolling more than 900 patients and following them for a maximum of 2.5 years.

The trials compared the efficacy and safety of Kesimpta against Aubagio (teriflunomide), an approved oral MS treatment. Collectively, the trials enrolled 1,882 people with RRMS or active SPMS who received either subcutaneous Kesimpta (20 mg) every four weeks or Aubagio tablets once daily, for up to 30 months.

In both trials, treatment with Kesimpta resulted in a significant decrease in patients’ annual relapse rates — by 51% in ASCLEPIOS I and 58% in ASCLEPIOS II — compared with Aubagio. Furthermore, the risk of disability worsening lasting at least three months was 34% lower with Kesimpta, and disability progression confirmed at six months was 32% lower. Kesimpta also outperformed Aubagio in reducing the number of new or enlarging lesions in the brain by more than 80%.

Ongoing trials

Novartis is currently running an open-label Phase 3 extension study (NCT03650114), called ALITHIOS, to collect long-term data on Kesimpta’s safety, tolerability, effectiveness, and health outcomes in adults who participated in previous Kesimpta trials.

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

The company also opened two Phase 3 open-label trials to assess the impact of switching from other MS therapies to Kesimpta following a relapse.

ARTIOS trial

One, called ARTIOS (NCT04353492), is enrolling people with relapsing MS — RRMS or SPMS — who move to Kesimpta from dimethyl fumarate or fingolimod, two FDA-approved oral MS therapies.

Dimethyl fumarate is marketed under the brand name Tecfidera, while fingolimod is sold as Gilenya; generics also are available for both medications.

ARTIOS is currently recruiting up to 550 eligible adults at 153 sites globally, including study locations in the U.S., Canada, Europe, Argentina, Australia, Mexico, and Russia.

OLIKOS trial

The other trial, OLIKOS (NCT04486716), expects to enroll about 100 people with relapsing MS who switch to Kesimpta from another anti-CD20 monoclonal antibody therapy, such as Genentech’s Ocrevus (ocrelizumab) or rituximab, which is commonly used off-label in MS. Participants are being recruited in the U.S. and Puerto Rico.

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

Infection risk

Kesimpta can decrease levels of infection-fighting antibodies, and this may increase the risk of infection. Antibody levels should be measured before starting on Kesimpta, and treatment should be delayed in individuals who have an active infection, until it is resolved. If patients experience recurring infections or develop a serious opportunistic infection, the medication may be discontinued.

People on Kesimpta should also not receive vaccines that contain live or live-attenuated viruses.

PML risk

A rare, serious viral infection of the brain called progressive multifocal leukoencephalopathy (PML) may occur with Kesimpta treatment.

PML is caused by infection with the JC virus, also called polyomavirus 2. This common virus is harmless except in people with weakened immune systems, where it can lead to inflammation and progressive damage to white matter, the part of the brain with myelinated nerve fibers.

Pregnancy risk

According to animal data, Kesimpta may cause harm to a developing fetus. Therefore, patients with the capacity to become pregnant are advised to use contraception while on Kesimpta and for six months after stopping the therapy. Patients who are breastfeeding or plan to breastfeed should inform their healthcare provider, as it is not clear if Kesimpta can pass into breast milk.