KESIMPTA resources
Don’t miss out on these resources to support you and your patients.
Prescribing information (external link)
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KESIMPTA®▼ (ofatumumab) mechanism of action
KESIMPTA®▼ (ofatumumab) is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features.1
Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) while receiving KESIMPTA and for 6 months after the last administration.1
For full safety information, please refer to KESIMPTA Summary of Product Characteristics (SmPC).1
Click the buttons below to learn more about the mechanism of action (MoA) of KESIMPTA
KESIMPTA is different by design
KESIMPTA is the first fully human B-cell targeting monoclonal antibody (mAb) in active RMS.1,2 KESIMPTA preferentially targets B-cells in lymph nodes with less delivered to the spleen, which may help preserve immunoglobulin G (IgG) levels (data from animal models).1,3–5 Watch the short video below to learn more.
The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown. The clinical relevance of these data are unknown.
How does multiple sclerosis (MS) develop?
MS is a complex, autoimmune condition defined by inflammation, demyelination and axonal damage in the central nervous system (CNS). This damage is caused by B-cells within the lymph nodes, which capture auto-antigens from neurons or their myelin sheaths and, upon presentation to T-cells, direct them to attack the body’s CNS tissue.6,7
To learn more about the pathogenesis of MS and the role of B-cells in the disease, watch this short video.
How does KESIMPTA work?
To learn about how KESIMPTA targets B-cell subsets that facilitate inflammation, and how it causes CD20-inducing lysis of these B-cells, watch this short video.1
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KESIMPTA is the first fully human B-cell targeting mAb in active RMS1,2
KESIMPTA has been shown to act on B-cells in MS patients, targeting them and inducing cell lysis1
KESIMPTA is an anti-CD20 monoclonal IgG1 antibody that acts on the immune system, by selectively targeting and binding to the CD20 protein.1 This protein is expressed on the surface of the majority of B-cells, making it a valuable target for precise MS treatment.8 KESIMPTA is thought to work by selectively binding to sites on both the small and the large extracellular loops of CD20 protein on B-cells8–10
The precise MoA by which KESIMPTA exerts its therapeutic effects is unknown.
Dose and frequency
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KESIMPTA dosing was designed to sustain B-cell depletion with a generally favourable benefit–risk balance.11–13
To find a generally favourable benefit–risk balance, the recommended 20 mg dose of KESIMPTA was carefully selected through dose modelling based on B-cell depletion and Phase II data, which concluded that once-monthly 20 mg subcutaneous (SC) dosing was comparably effective with generally fewer side effects than higher SC doses.11–13
Initial dosing starts at Weeks 0, 1 and 2, followed by subsequent monthly dosing starting at Week 4.1
How does KESIMPTA impact B-cell depletion in active RMS?
Induced lysis of CD20+ B-cells results in depletion through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). KESIMPTA has been shown to induce target cell death in both high and low CD20-expressing cells.1
The selective MoA and precise delivery arising from the SC MoA enables preferential depletion of B-cells in the lymph nodes. The preservation of B-cells in the spleen, as demonstrated by preclinical evidence, may contribute to immune function.3–5
Rapid B-cell depletion as early as Week 11,14
ASCLEPIOS I and II (pooled analysis): Continuous therapeutic effect with KESIMPTA monthly dosing14
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Near complete depletion by Week 4, sustained from Week 2 up to Week 96.1,14
KESIMPTA demonstrated continuous therapeutic effect between monthly doses14
Adapted from Hauser SL, et al. 2020.14
In the RMS clinical studies using KESIMPTA 20 mg every 4 weeks, after an initial dose regimen of 20 mg on Days 1, 7, and 14, administration resulted in a rapid and sustained reduction of B-cells to below LLN (defined as 40 cells/µL) as early as two weeks after treatment initiation. Before initiation of the maintenance phase starting at Week 4, total B-cell levels of <10 cells/µL were reached in 94% of patients, increasing to 98% of patients at Week 12, and were sustained for as long as 120 weeks (i.e. while on study treatment).1
Click here to learn about the efficacy of KESIMPTA in eligible patients
How long does B-cell repletion take after KESIMPTA discontinuation in RMS?
In the event of treatment discontinuation, B-cell repletion has also been studied in predictive models.1
B-cell repletion: Data from RMS Phase III trials indicate a median time to B-cell recovery to LLN or baseline value of 24.6 weeks post-treatment discontinuation1
Simulated median and 90% prediction interval*15
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KESIMPTA demonstrated continuous therapeutic effect between monthly doses14,15
Adapted from Yu H, et al. 2022.15
PK B-cell modelling and simulation for B-cell repletion corroborate these data, predicting a median time to B-cell recovery to LLN (40 cells/μL) of 23 weeks post-treatment discontinuation.1
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Learn about patient self-administration of KESIMPTA on the dosing and administration page
*Based on pharmacokinetic B-cell modelling (B-cell model: An indirect response model to describe the stimulation of B-cell lysis by free ofatumumab concentrations) of B-cell counts from 1486 patients with SC KESIMPTA administration and 25 patients with intravenous KESIMPTA administration across 5 pooled studies (MIRROR, OMS115102, ASCLEPIOS I & II and APLIOS). Simulation is for SC route with pre-filled syringe and using Phase Ill dosage regimen.15 KESIMPTA is not licensed for intravenous administration; please see the SmPC for more details.
ADCC, antibody-dependent cellular cytotoxicity; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CNS, central nervous system; HCP, healthcare professional; IgG, immunoglobulin G; LLN, lower limit of normal; mAb, monoclonal antibody; MoA, mechanism of action; MS, multiple sclerosis; PK, pharmacokinetics; RMS, relapsing multiple sclerosis; SC, subcutaneous; SmPC, summary of product characteristics.
References
KESIMPTA (ofatumumab) Summary of Product Characteristics.
Hauser SL, et al. Neurol Ther 2023;12(5):1491–1515.
Theil D, et al. Front lmmunol 2019;10:1340.
Huck C, et al. J Neuroimmune Pharmacol 2019;14(4):709–719.
Torres JB, et al. Front Immunol 2022;13:814064.
Pender MP, et al. Curr Allergy Asthma Rep 2007;(4):285–292.
Archelos JJ, et al. Ann Neurol 2000;47:694–706.
Zhang B. mAbs 2009;1(4):326–331.
Gupta IV & Jewell RC. Ann N Y Acad Sci 2012;1263:43–56.
Martin R, et al. Eur J Immunol 2016;46:2078–2090.
Sorensen PS, et al. Neurology 2014;82:573–581.
Bar-Or A, et al. Neurology 2018;90:e1805–e1814.
Savelieva M, et al. Poster P5.348. American Academy of Neurology (AAN). 22–28 April 2017, Boston, MA.
Hauser SL, et al. Poster P7.1-013. American Academy of Neurology (AAN). 25 April–1 May 2020.
Yu H, et al. CNS Drugs 2022;36(3):283–300.
Novartis Data on File. Ofatumumab (OFA22). June 2024.
UK | July 2026 | FA-11673031
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report, or alternatively email [email protected] or call 01276 698370.
