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KESIMPTA®▼ (ofatumumab) is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis with active disease defined by clinical or imaging features.
For full safety information, please refer to the GB KESIMPTA Summary of Product Characteristics (SmPC) and NI KESIMPTA Summary of Product Characteristics (SmPC).
KESIMPTA is different by design
KESIMPTA is the only subcutaneously delivered B-cell treatment in the UK. It is thought to work by selectively binding to sites on both the small and large extracellular loops of CD20.1–4
KESIMPTA is the first fully human B-cell targeting mAb1–4
KESIMPTA is a targeted B-cell therapy.1,2,5–7 Preclinical evidence shows subcutaneous delivery preferentially targets B cells in the lymph nodes5,6 and spares B cells in the spleen, which may help maintain immune function7
The recommended dose is 20 mg KESIMPTA with initial dosing at Weeks 0, 1 and 2, followed by subsequent monthly dosing, starting at Week 4. The 20 mg dose was chosen through dose modelling based on B-cell depletion results and Phase II data8–10
The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown. The clinical relevance of these data is unknown.
Click on the tabs to learn more about the mechanism of action of KESIMPTA.
KESIMPTA has been shown to act on B-cells in MS patients, targeting them and inducing cell lysis1,2
To learn about the pathogenesis of MS and the role of B-cells in the disease, watch this short video.
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.
IgG serum levels
In ALITHIOS, mean serum IgG levels remained stable and above the LLN in KESIMPTA-treated patients for up to 5 years11
Mean serum IgG levels remained above the LLN (5.65 g/L) in 98% of patients (data cut-off: September 2022)
Adapted from Cohen JA, et al. 2023.11
The overall rate of AEs and severe AEs remained consistent with ASCLEPIOS. Treatment interruption/discontinuation* was reported in 3 (0.2%)/4 (0.2%) patients due to low IgG.
IgM serum levels
In ALITHIOS, a decrease in mean IgM levels was observed for KESIMPTA-treated patients but remained above the LLN for up to 5 years11
Mean serum levels of IgM decreased in both groups, but remained above the LLN (0.40 g/L) in 69.4% of patients (data cut-off: September 2022)
Adapted from Cohen JA, et al. 2023.11
Treatment interruption/discontinuation* was reported in 202 (10.3%)/71 (3.6%) patients due to low IgM.
NO ASSOCIATION BETWEEN DECREASED IgG or IgM LEVELS AND RISK OF SERIOUS INFECTIONS WAS OBSERVED11
B-cell depletion
Dosing period from ASCLEPIOS I and II (pooled analysis)12
Adapted from Hauser SL, et al. 2020.12
As early as Week 1 of KESIMPTA treatment, B-cell reduction was observed, with close to complete depletion by Week 412
B-cell repletion
Simulated median and 90% prediction interval†13
Adapted from Yu H, et al. 2020.13
RMS Phase III clinical studies indicate a median time to B-cell recovery to LLN or baseline value of 24.6 weeks post-treatment discontinuation1,2
*Per core and extension study protocols, investigators were required to interrupt study treatment if IgM levels fell below 10% LLN or IgG levels fell below 20% LLN. The requirement to interrupt treatment due to low IgM or IgG levels was removed with protocol amendment 2 for study COMB157G2399 and is left to the discretion of the investigator.
†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 subcutaneous route with pre-filled syringe and using Phase III dosage regimen.
AE, adverse event; CD, cluster of differentiation; IgG, immunoglobulin G; IgM, immunoglobulin M; LLN, lower limit of normal; mAb, monoclonal antibody; MoA, mechanism of action; MoD, mechanism of disease; MS, multiple sclerosis; SC, subcutaneous; SE, standard error.
References
- KESIMPTA (ofatumumab) Summary of Product Characteristics, Great Britain; March 2023.
- KESIMPTA (ofatumumab) Summary of Product Characteristics, Northern Ireland; March 2023.
- National Multiple Sclerosis Society. Medications. Available from: https://www.nationalmssociety.org/Treating-MS/Medications [Accessed August 2023].
- Gupta IV, Jewell RC. Ann N Y Acad Sci 2012;1263:43–56.
- Torres JB, et al. Poster P2.2-052 presented the American Academy of Neurology (AAN). May 2019.
- Huck C, et al. J Neuroimmune Pharmacol 2019;14(4):709–719.
- Theil D, et al. Front lmmunol 2019;10:1340.
- 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 presented at the American Academy of Neurology (AAN). April 2017.
- Cohen JA, et al. Poster P8.004 presented at the American Academy of Neurology (AAN). April 2023.
- Hauser SL, et al. Poster P7.1–013. Presented at: American Academy of Neurology; 25 April–1 May, 2020; Toronto, Canada.
- Yu H, et al. CNS Drugs 2022;36(3):283–300.
