Kesimpta (ofatumumab) is a disease-modifying treatment by Novartis for adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis.1
The treatment is approved by the US Food and Drug Administration (FDA) and the European Commission (EC).2,3
It is a subcutaneous injection that can be self-administered by patients at home. Three initial 20 mg doses, at weeks 0, 1, and 2, are followed by once-monthly injections.1
Kesimpta Mechanism of Action
Multiple sclerosis is a progressive disease characterized by an immune system attack on the central nervous system (CNS). It is not fully understood how B lymphocytes contribute to the development of MS, but it is thought they may be involved in presenting antigens to T lymphocytes, transporting antigens from tissues to secondary lymphoid organs, secreting pro-inflammatory cytokines, and producing pathogenic antibodies.4 These processes could be contributing to demyelination within the inflamed CNS.5 Therefore, depleting B lymphocytes could reduce disease activity.
Get detailed prescribing information on the Kesimpta monograph page on Rare Disease Advisor.
Kesimpta is a monoclonal antibody that binds to the CD20 docking site on B lymphocytes. This results in antibody-dependent cellular cytolysis and complement-mediated lysis destroying the B lymphocytes and possibly reducing the damage they cause to the myelin sheath, resulting in symptom reduction and slower disease progression.6
Warnings, Precautions, and Adverse Reactions
Kesimpta can cause serious side effects, including infections, progressive multifocal leukoencephalopathy (PML), and reactivation of hepatitis B virus (HBV) infection .7 It can also cause injection site reactions, such as redness, swelling, itching, and pain as well as fever, headache, muscle pain, chills, and fatigue. Kesimpta should not be used by patients with active HBV infections.
Patients should be given any required live or live-attenuated vaccines at least 4 weeks before the start of Kesimpta treatment. They should not be given these types of vaccines while being treated with Kesimpta.
It is not known whether Kesimpta can cause harm to the fetus or passes into breast milk. Female patients who are of childbearing age should use contraception while on Kesimpta treatment and for 6 months following discontinuation.
Efficacy in Clinical Trials
The FDA approved Kesimpta based on the results of 2 identical design phase 3 clinical trials.
The trials, ASCLEPIOS I and ASCLEPIOS II, were randomized, double-blind, double-dummy, parallel-group studies that compared the safety and efficacy of Kesimpta to that of Aubagio® (teriflunomide) in patients with relapsing MS.8,9 The primary endpoint of the studies was the annualized relapse rate (ARR). The secondary endpoints included 3- and 6-month confirmed disability worsening, the number of gadolinium-enhancing T1 lesions, the number of new or enlarging T2 lesions, and the annualized rate of brain volume loss.
The trials enrolled 1882 patients aged 18 to 55 years with an Expanded Disability Status Scale (EDSS) score between 0 and 5.5 and randomly assigned them to either subcutaneous Kesimpta or oral Aubagio for up to 30 months.
The results showed that Kesimpta treatment was associated with a lower ARR compared to Aubagio.10 Moreover, the percentage of patients with disability worsening confirmed at 3 and 6 months were lower in the Kesimpta groups compared to the Aubagio group. Kesimpta treatment also led to significant reductions in both gadolinium-enhancing T1 lesions and new or enlarging T2 lesions.
Ongoing Studies for Kesimpta
Another phase 3 clinical trial is currently testing the long-term safety, tolerability, and effectiveness of Kesimpta.11 The open-label, single-arm, multicenter extension study, called ALITHIOS, is currently recruiting 2010 participants aged 18 years or older who have completed an ASCLEPIOS trial, at 292 sites across the world.
The primary endpoint of the trial is the number of patients who experience an adverse event or have abnormal laboratory, vital, and/or echocardiogram results, and positive suicidality outcomes. Secondary outcome measures include the number of relapses per year, confirmed 3- and 6-month disability worsening, and changes in EDSS scores, brain volume, and T2, and gadolinium-enhancing lesions.
This trial also includes a vaccination substudy, the purpose of which is to assess the effects of Kesimpta on the development of antibody responses to selected vaccines in patients with relapsing MS.
The trial is estimated to be completed in October 2028.
Two other ongoing trials are assessing the effects of switching to Kesimpta from other disease-modifying treatments for MS.12,13 The first, called ARTIOS, is recruiting participants previously treated with Tecfidera® or Gilenya®, and the other, called OLIKOS, is recruiting participants who are switching to Kesimpta from Ocrevus®.
1. Kesimpta. Novartis. Accessed June 14, 2021.
2. Kesimpta. Package insert. Novartis; 2009. Updated August 2020. Accessed June 14, 2021.
3. Kesimpta. European Medicines Agency. Accessed June 14, 2021.
4. Sospedra M. B cells in multiple sclerosis. Curr Opin Neurol. 2018;31(3):256-262. doi:10.1097/WCO.000000000000563
5. Lehmann-Horn K, Kronsbein HC, Weber MS. Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges. Ther Adv Neurol Disord. 2013; 6(3): 161–173. doi:10.1177/1756285612474333
6. Kesimpta. National Multiple Sclerosis Society. Accessed June 14, 2021.
7. Understanding side effects. Novartis. Accessed June 14, 2021.
8. Efficacy and safety of ofatumumab compared to teriflunomide in patients with relapsing multiple sclerosis (ASCLEPIOS I). ClinicalTrials.gov. June 7, 2016. Updated May 12, 2021. Accessed June 14, 2021.
9. Efficacy and safety of ofatumumab compared to teriflunomide in patients with relapsing multiple sclerosis. (ASCLEPIOS II). ClinicalTrials.gov. June 7, 2016. Updated May 12, 2021. Accessed June 14, 2021.
10. Hauser S, Bar-Or A, Cohen J, et al. Ofatumumab versus teriflunomide in multiple sclerosis. N Engl J Med. 2020;6;383(6):546-557. doi:10.1056/NEJMoa1917246
11. Long-term safety, tolerability and effectiveness study of ofatumumab in patients with relapsing MS (ALITHIOS). ClinicalTrials.gov. August 28, 2018. Updated May 11, 2021. Accessed June 14, 2021.
12. An open-label study evaluating ofatumumab treatment effectiveness and PROs in subjects with RMS transitioning from dimethyl fumarate or fingolimod to ofatumumab (ARTIOS). ClinicalTrials.gov. April 20, 2020. Updated June 1, 2021. Accessed June 14, 2021.13. A single arm study evaluating the efficacy, safety and tolerability of ofatumumab in patients with relapsing multiple sclerosis (OLIKOS). ClinicalTrials.gov. July 27, 2020. Updated June 1, 2021. Accessed June 14, 2021.
Reviewed by Kyle Habet, MD, on 7/1/2021.