The U.S. Food and Drug Administration (FDA) approved Kesimpta in August 2020 for the treatment of adults with relapsing multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
According to Novartis, which manufactures Kesimpta, this is the first MS therapy targeting B-cells that the FDA approved and that can be administered at home. The treatment is given once per month, via under-the-skin injection using the Sensoready Pen.
Other regulatory filings seeking approval for Kesimpta as an MS treatment elsewhere in the world are ongoing; a decision in the European Union is expected in the first half of 2021.
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 protein layer that insulates nerve fibers.
The exact mode of action by which Kesimpta alters relapse and remission in MS is still uncertain. Researchers know that the treatment targets B-cells by binding to the CD20 protein found on their surface. They think 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 companies 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 in 2011 for 48 weeks, or just less than one year. The results showed a considerable reduction in the formation of brain plaques — 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 plaque formation. The researchers published these results in the scientific journal Neurology.
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. The participants were randomly selected to receive one of five treatments: a placebo, 3 mg, 30 mg, or 60 mg of Kesimpta every 12 weeks, or 60 mg of Kesimpta every four weeks. All of the patients continued in the study for 24 weeks and until B-cell depletion (or destruction).
Ofatumumab was able to deplete the B-cells quickly, depending on the dose and regimen, and effectively reduced the formation of new brain plaques relative to 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 1,881 adults with RRMS or active SPMS were enrolled in the trials. The participants received either Kesimpta every four weeks or Aubagio once daily.
The study assessed the number of confirmed relapses in 12 months, recorded for up to 2.5 years. The disability worsening showed a risk reduction of 34.4% at three months, and 32.5% at six months with Kesimpta, compared with Aubagio. Disability improvement at six months also showed a favorable trend for Kesimpta, but the results were not statistically significant.
Kesimpta treatment led to a 97.5% relative reduction in the number of T1 lesions in ASCLEPIOS I, and 93.8% 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 occurred in 83.6% of patients on ofatumumab, and 84.2% of patients receiving Aubagio. There were no significant differences between the two groups with regard to the rate of infections (2.5% with Kesimpta vs. 1.8% with Aubagio) or malignancies (0.5% with Kesimpta vs. 0.3% with Aubagio).
Ongoing clinical trials
A Phase 3 clinical trial (NCT03650114) is now assessing the long-term safety, tolerability, effectiveness, and health outcomes of Kesimpta in adults who participated in previous studies. These patients are currently being recruited at various locations across the world.
Due to end in January 2028, this trial also includes a sub-study evaluating the antibody response to certain vaccines in eligible MS patients. Because Kesimpta leads to B-cell depletion, it can affect a person’s response to vaccinations. Thus, patients should not receive vaccinations during or shortly after Kesimpta treatment.
The FDA also approved ofatumumab, under the brand name Arzerra, to treat chronic lymphocytic leukemia. Researchers also are investigating it as a potential treatment for other blood cancers, such as follicular lymphoma.
Last updated: Aug. 21, 2020
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