Kesimpta (ofatumumab) is an antibody that targets the CD20 protein, found on the surface of certain types of immune cells called B-cells, that has been shown to reduce relapse rates and the risk of disability progression for people with multiple sclerosis (MS).
The U.S. Food and Drug Administration (FDA) approved Kesimpta in August 2020 for treating adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
In March 2021, the European Commission approved Kesimpta for the treatment of relapsing MS in adults with active disease, two months after a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use. The therapy also is approved in Canada, Switzerland, Australia, and Japan, among other countries.
The Danish biotechnology company Genmab first developed the treatment and licensed it to GlaxoSmithKline. Novartis acquired the rights to ofatumumab in 2015.
According to Novartis, Kesimpta is the first MS therapy targeting B-cells that can be self-administered at home. The treatment is given once per month, via under-the-skin (subcutaneous) injection using a patient-friendly autoinjector pen called the Sensoready Pen.
How does Kesimpta work?
MS is an autoimmune disease in which the body’s immune system mistakenly attacks and damages the myelin sheath, the protective layer that insulates nerve fibers.
The exact mode of action by which Kesimpta alters disease activity in MS is still uncertain. Researchers know that the treatment targets B-cells by binding to the CD20 protein found on their surface. It is believed that this leads to a decrease in the number of these immune cells that attack the myelin sheath.
Kesimpta in clinical trials
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) with a small group of 38 RRMS patients tested different doses of Kesimpta for 48 weeks, or just less than one year. The therapy was given through intravenous (into-the-vein) infusions. The results showed a considerable reduction in the formation of brain lesions — areas where the myelin is stripped off of the nerves — along with lower numbers of autoimmune B-cells. The treatment also appeared to suppress new lesion formation.
These findings paved the way for a second larger, multicenter, double-blind, placebo-controlled Phase 2 trial (NCT01457924) called MIRROR, which enrolled 232 people with RRMS. Participants were randomly selected to receive a placebo or one of four Kesimpta dosing regimens: 3 mg, 30 mg, or 60 mg of Kesimpta every 12 weeks (about three months), or 60 mg of Kesimpta every four weeks (about one month). The treatment was given as a subcutaneous formulation (injected under the skin) during a total of 24 weeks (just less than six months).
Ofatumumab was able to deplete B-cells quickly, depending on the dose and regimen, and effectively reduced the formation of new brain lesions compared with the placebo, the results showed. The researchers recorded no new or unexpected safety findings.
Two randomized, double-blind Phase 3 studies, ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231), compared the efficacy and safety of Kesimpta against Aubagio (teriflunomide), an oral MS treatment approved by the FDA. A total of 1,882 adults with RRMS or active SPMS were enrolled in the trials and received either Kesimpta (20 mg subcutaneous) every four weeks or Aubagio (14 mg oral tablet) once daily.
Both trials met their primary goal, as treatment with Kesimpta resulted in a significant decrease in patients’ annual relapse rates — by 51% in ASCLEPIOS I and by 58% in ASCLEPIOS II — compared with Aubagio.
Furthermore, the relative risk of disability worsening was 34% lower at three months and 32% lower at six months with Kesimpta, compared with Aubagio. A lessening in disability at six months also showed a favorable trend for Kesimpta, but the results were not statistically significant.
Kesimpta treatment led to a 97% relative reduction in the number of T1 MRI lesions (which indicate areas of ongoing inflammation) in ASCLEPIOS I, and 94% in ASCLEPIOS II, relative to Aubagio. These findings led the researchers to conclude that Kesimpta treatment is superior to Aubagio in treating people with relapsing forms of MS.
Adverse events in the ASCLEPIOS trials occurred in 83.6% of patients on Kesimpta, and 84.2% of patients receiving Aubagio. There were no significant differences between the two groups with regard to the rate of infections or malignancies.
The most common side effects associated with Kesimpta are upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions.
No cases of progressive multifocal leukoencephalopathy (PML) — a brain infection previously associated with other MS therapies — were reported in clinical trials with Kesimpta.
Ongoing clinical 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 studies. The trial is following about 90% of the ASCLEPIOS participants and is recruiting patients at various locations across the world. More information is available here.
Due to be completed in 2028, this trial also includes a sub-study evaluating the antibody response to certain vaccines in eligible MS patients. This is of interest because Kesimpta kills B-cells, the immune cell primarily responsible for antibody production, and there have been reports of other B-cell targeting therapies interfering with vaccine-induced immunity.
Novartis also opened two open-label trials to assess the impact of switching from other MS therapies to Kesimpta.
The Phase 3 trial ARTIOS (NCT04353492) is enrolling people with relapsing MS who move to Kesimpta from dimethyl fumarate or fingolimod, two FDA-approved oral MS therapies marketed under the brand names Tecfidera, by Biogen, and Gilenya, by Novartis. (Generics also are available). ARTIOS is seeking up to 550 eligible adults at sites in the U.S., Australia, and Europe. Additional information can be found here.
The other open-label 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). Participants are being recruited in the U.S. and Puerto Rico. For more information, see the trial page here.
In addition, Novartis is exploring other avenues for Kesimpta’s clinical development, including plans to test the medication in children with MS.
Other information
The FDA also approved ofatumumab, under the brand name Arzerra, to treat chronic lymphocytic leukemia, a blood cancer that typically develops in B-cells.
Last updated: March 30, 2021
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