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Mechanism of Action

KESIMPTA is a targeted and precisely delivered B-cell therapy for relapsing multiple sclerosis1-3

Watch the mechanism of action (MOA) video

KESIMPTA is thought to work by selectively binding to sites on both the small and large extracellular loops of CD20.4

KESIMPTA causes CD20+ B cells to be vulnerable to both immediate and delayed B-cell lysis by mechanisms such as complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity4

Body with B cells as red dots

B cells in the lymph nodes

Preclinical studies showed that SC delivery preferentially targeted B cells in the lymph nodes2,3,5

 

Body with dotted outline and B cell as a red dot in the spleen

B cells in the spleen

SC delivery of KESIMPTA is thought to spare B cells in the spleen to help maintain immune function, based on preclinical evidence1

 

The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown.

The clinical relevance of these data is unknown.

What is the significance of targeting CD20 in MS?

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See expert perspectives on the KESIMPTA MOA

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“What’s unique about KESIMPTA? There are studies that suggest the subcutaneous delivery allows the monoclonal antibodies to get to lymph nodes and lymphoid tissues in a more marked way...knocking out B cells in those lymph nodes.” Dr Patricia K Coyle MD, FAAN, FANA

*Dr. Coyle is a paid consultant for Novartis.

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LLN, lower limit of normal; MS, multiple sclerosis; SC, subcutaneous.

References: 1. Theil D, Smith P, Huck C, et al. Imaging mass cytometry and single-cell genomics reveal differential depletion and repletion of B-cell populations following ofatumumab treatment in cynomolgus monkeys. Front lmmunol. 2019;10:1340. doi:10.3389/fimmu.2019.01340 2. Torres JB, Roodselaar J, Sealey M, et al. Distribution and efficacy of ofatumumab and ocrelizumab in humanized-CD20 mice following subcutaneous or intravenous administration. P2.2-052. Presented at: 71st American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. 3. Huck C, Leppert D, Wegert V, et al. Low-dose subcutaneous anti-CD20 treatment depletes disease relevant B cell subsets and attenuates neuroinflammation. J Neuroimmune Pharmacol. 2019;14(4):709-719. 4. Gupta IV, Jewell RC. Ofatumumab, the first human anti-CD20 monoclonal antibody for the treatment of B cell hematologic malignancies. Ann NY Acad Sci. 2012;1263(1):43-56. 5. Kesimpta. Prescribing information. Novartis Pharmaceuticals Corp. 6. Hauser SL, Bar-Or A, Cohen JA, et al. B-cell depletion and efficacy outcomes with ofatumumab: subgroup analysis from the pooled phase 3 ASCLEPIOS I and II trials. Poster P7.1-013. Presented at: 72nd American Academy of Neurology Annual Meeting; April 25-May 1, 2020; Toronto, Canada. 7. Hauser SL, Bar-Or A, Cohen JA, et al; ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis. Supplemental appendix. N Engl J Med. 2020;383(6):546-557.