MECHANISM OF ACTION

Targeted and precisely delivered B-cell therapy

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This animated video brings the immune system to life with a molecule's eye view of KESIMPTA

KESIMPTA® (ofatumumab) mechanism of action

KESIMPTA is thought to work by selectively binding to sites on both the small and large extracellular loops of CD20.1

  • 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 cytotoxicity1

When delivered subcutaneously, KESIMPTA is thought to promote preferential depletion of B cells in the lymph nodes.2,3

Preclinical evidence suggests KESIMPTA may spare B cells in the spleen that help maintain immune function.4,5

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

DIGITAL EDUCATION LAB

Watch a video with an expert perspective on the KESIMPTA mechanism of action

Targeted and Precisely Delivered Therapy: Understanding KESIMPTA Mechanism of Action

Watch a video with an expert perspective on
the KESIMPTA mechanism of action

Targeted and Precisely Delivered Therapy:
Understanding KESIMPTA Mechanism of Action

GO TO VIDEO EXPLORE MORE EXPERT PERSPECTIVES
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EXPLORE MORE EXPERT PERSPECTIVES

B-cell depletion

Subcutaneous, targeted, and precisely delivered therapy that provides rapid B-cell depletion6,7

B-cell depletion sustained over the dosing period

B-cell depletion sustained over

the dosing period

This chart shows B-cell depletion sustained over the dosing period.

  • Reduction in B cells was seen as early as 1 week after treatment initiation2

  • The CD19+ B-cell counts remained below LLN for approximately 97% of patients in ASCLEPIOS I and 92% of patients in ASCLEPIOS II from 12 weeks through 120 weeks while on KESIMPTA treatment2

B-cell repletion upon
discontinuation2

  • Data from Studies 1 and 2 indicate a median time to B-cell recovery to either LLN or baseline value of 24.6 weeks post-treatment discontinuation. PK and PD modeling and simulation for B-cell repletion corroborate these data, predicting median time to B-cell recovery to LLN of 23 weeks post-treatment discontinuation

  • Modeling and simulation for B-cell repletion corroborates these data, predicting median time to B-cell recovery of 40 weeks post-treatment discontinuation

'I knew I needed to make a change to have a better chance at beating RMS. I'm glad my doctor agreed.' - Kristin: mother, real estate agent, Kesimpta patient.

When my neurologist provided the data for me for
KESIMPTA, it gave me hope.

Kristin: mom, real estate agent, KESIMPTA patient*

*Actual KESIMPTA patient who was compensated for their time. Individual results may vary.

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IgG=immunoglobin G; LLN=lower limit of normal; MOA=mechanism of action; RMS=relapsing multiple sclerosis; SC=subcutaneous.

References: 1. 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. 2. Kesimpta [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 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. 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. Poster presented at: American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. 5. 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;10:1-11. 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. P7.1-013. Poster presented at: American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. 7. Hauser SL, Bar-Or A, Cohen JA, et al; for the ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis [supplemental appendix]. N Engl J Med 2020;383(6):546-557.

IMPORTANT SAFETY INFORMATION

Contraindication: KESIMPTA is contraindicated in patients with active hepatitis B virus infection.

WARNINGS AND PRECAUTIONS

Infections: An increased risk of infections has been observed with other anti-CD20 B-cell depleting therapies. KESIMPTA has the potential for an increased risk of infections

INDICATION

KESIMPTA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

SEE IMPORTANT SAFETY INFORMATION

INDICATION

KESIMPTA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

IMPORTANT SAFETY INFORMATION

Contraindication: KESIMPTA is contraindicated in patients with active hepatitis B virus infection.

WARNINGS AND PRECAUTIONS

Infections: An increased risk of infections has been observed with other anti-CD20 B-cell depleting therapies. KESIMPTA has the potential for an increased risk of infections including serious bacterial, fungal, and new or reactivated viral infections; some have been fatal in patients treated with other anti-CD20 antibodies. The overall rate of infections and serious infections in KESIMPTA-treated patients was similar to teriflunomide-treated patients (51.6% vs 52.7%, and 2.5% vs 1.8%, respectively). The most common infections reported by KESIMPTA-treated patients in relapsing MS (RMS) trials included upper respiratory tract infection (39%) and urinary tract infection (10%). Delay KESIMPTA administration in patients with an active infection until resolved.

Consider the potential increased immunosuppressive effects when initiating KESIMPTA after an immunosuppressive therapy or initiating an immunosuppressive therapy after KESIMPTA.

Hepatitis B Virus: Reactivation: No reports of hepatitis B virus (HBV) reactivation in patients with MS treated with KESIMPTA. However, HBV reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred in patients treated with ofatumumab at higher intravenous doses for chronic lymphocytic leukemia (CLL) than the recommended dose in MS and in patients treated with other anti-CD20 antibodies.

Infection: KESIMPTA is contraindicated in patients with active hepatitis B disease. Fatal infections caused by HBV in patients who have not been previously infected have occurred in patients treated with ofatumumab at higher intravenous doses for CLL than the recommended dose in MS. Perform HBV screening in all patients before initiation of KESIMPTA. Patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], should consult liver disease experts before starting and during KESIMPTA treatment.

Progressive Multifocal Leukoencephalopathy: No cases of progressive multifocal leukoencephalopathy (PML) have been reported for KESIMPTA in RMS clinical studies; however, PML resulting in death has occurred in patients being treated with ofatumumab at higher intravenous doses for CLL than the recommended dose in MS. In addition, JC virus infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies. If PML is suspected, withhold KESIMPTA and perform an appropriate diagnostic evaluation. If PML is confirmed, KESIMPTA should be discontinued.

Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines at least 4 weeks and, whenever possible at least 2 weeks prior to starting KESIMPTA for inactivated vaccines. The safety of immunization with live or live-attenuated vaccines following KESIMPTA therapy has not been studied. Vaccination with live or live-attenuated vaccines is not recommended during treatment and after discontinuation until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with KESIMPTA During Pregnancy. For infants whose mother was treated with KESIMPTA during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines. If the B-cell count has not recovered in the infant, do not administer the vaccine as having depleted B-cells may pose an increased risk in these infants.

Injection-Related Reactions: Injection-related reactions with systemic symptoms occurred most commonly within 24 hours of the first injection, but were also observed with later injections. There were no life-threatening injection reactions in RMS clinical studies.

The first injection of KESIMPTA should be performed under the guidance of an appropriately trained health care professional. If injection-related reactions occur, symptomatic treatment is recommended.

Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections and after discontinuation of therapy until B-cell repletion. Consider discontinuing KESIMPTA therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Fetal Risk: Based on animal data, KESIMPTA can cause fetal harm due to B-cell lymphopenia and reduce antibody response in offspring exposed to KESIMPTA in utero. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. Advise females of reproductive potential to use effective contraception while receiving KESIMPTA and for at least 6 months after the last dose.

Most common adverse reactions (>10%) are upper respiratory tract infection, headache, injection-related reactions, and local injection-site reactions.

Please see full Prescribing Information, including Medication Guide.

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