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-...

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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.

Mechanism of Action

Make KESIMPTA your 1st choice for RMS Make KESIMPTA your 1st choice for RMS

Targeted B-Cell Therapy

A targeted and precisely delivered B-cell therapy1-5

Cell surface view cell surface view CELL SURFACE VIEW

KESIMPTA is thought to work by selectively binding to sites on both the small and large extracellular loops of CD20.2

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

KESIMPTA binding to CD20 induces lysis of B-cells1

Cell view cell view CELL VIEW

KESIMPTA causes CD20+ B-cells to be vulnerable to both immediate and delayed B-cell lysis by mechanisms such as complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).2

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

The subcutaneous administration of KESIMPTA promotes specific targeting of the lymph nodes1,3

Organ view organ view ORGAN VIEW

When delivered subcutaneously, KESIMPTA is thought to promote preferential depletion of B-cells in the lymph nodes. Preclinical evidence suggests KESIMPTA may preserve B-cells in the spleen that help maintain immune function.4,5

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

Cell surface view Cell view Organ view
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B-Cell Depletion

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

B-cell depletion sustained over the dosing period

Chart: B-cell depletion sustained below 8 cells/µL over dosing period Chart: B-cell depletion sustained below 8 cells/µL over dosing period
  • Reduction in B-cells was seen as early as 1 week after treatment initiation1
  • 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 treatment1

B-Cell Repletion Upon Discontinuation1

  • Data from RMS clinical studies indicate B-cell recoveries over the LLN in at least 50% of patients in 24 to 36 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
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LLN=lower limit of normal; RMS=relapsing multiple sclerosis.

References:

1. Kesimpta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020.
2. 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.
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. Poster P2.2.052. 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. Poster P7.1-013. 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.

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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