Drug Safety-related Labeling Changes (SrLC)

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KESIMPTA (BLA-125326)

(OFATUMUMAB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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04/01/2026 (SUPPL-84)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Infections

Additions and/or revisions underlined:

Vaccination of Infants Born to Mothers Treated with KESIMPTA During Pregnancy

In infants of mothers treated with KESIMPTA during pregnancy, do not administer live or live-attenuated vaccines before confirming the B-cell count is within normal range. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

Inactivated vaccines may be administered, as indicated, prior to confirming the B-cell count is within normal range, but an assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted.

5.5 Fetal Risk

Additions and/or revisions underlined:

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 pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception while receiving KESIMPTA and for at least 6 months after the last dose [see Use in Specific Populations (8.1)].

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

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No teratogenicity was observed after intravenous administration of ofatumumab to pregnant monkeys during organogenesis. However, increased mortality, depletion of B-cell populations, and impaired immune function were observed in the offspring, in the absence of maternal toxicity, at plasma levels higher than that in humans (see Data).

Although there are no data on ofatumumab, monoclonal antibodies can be actively transported across the placenta, and ofatumumab may cause immunosuppression in the in utero-exposed infant (see Clinical Considerations).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Clinical Considerations

Fetal/Neonatal adverse reactions

Transport of endogenous IgG antibodies across the placenta is low in the first trimester and increases as pregnancy progresses and peaks during the third trimester. Transient peripheral B-cell depletion and lymphocytopenia have been observed in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. B-cell levels in infants following maternal exposure to KESIMPTA have not been adequately studied in clinical trials. The potential duration of B-cell depletion in infants exposed to ofatumumab in utero, and the impact of B-cell depletion on the safety and effectiveness of vaccines, are unknown. Avoid administering live vaccines to neonates and infants exposed to KESIMPTA in utero before confirming B-cell count is within normal range [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].

Data

Animal Data

In the embryo-fetal development (EFD) study, intravenous administration of ofatumumab (weekly doses of 0, 20, or 100 mg/kg) to pregnant monkeys during the period of organogenesis (gestation days 20 to 50) resulted in no adverse effects on embryofetal development; however, B-cell depletion was observed in fetuses at both doses when assessed on gestation day 100. Plasma exposure (Cavg) at the no-effect dose (100 mg/kg) for adverse effects on embryofetal development was greater than 5000 times that in humans at the recommended human maintenance dose of 20 mg. A no-effect dose for effects on B-cells was not identified; plasma exposure (Cavg) at the low-effect dose (20 mg/kg) was approximately 780 times that in humans at the recommended human maintenance dose (RHMD) of 20 mg/month.

In the enhanced pre- and post-natal development (ePPND) study, intravenous administration of ofatumumab (5 weekly doses of 0, 10, and 100 mg/kg, followed by biweekly doses of 0, 3, and 20 mg/kg) to pregnant monkeys from gestation day 20 until birth resulted in no adverse effects on the development of the offspring. However, postnatal death, B-cell depletion, and impaired immune function were observed in the offspring at the high dose of 100/20 mg/kg. The deaths were considered secondary to B-cell depletion. Plasma exposure (Cavg) in dams at the no-effect dose (100/20 mg/kg) for adverse developmental effects was approximately 500 times that in humans at RHMD. A no-effect level for mortality and immune effects in offspring was not established because of the limited number of evaluable offspring at the low dose (10/3 mg/kg).

8.3 Females and Males of Reproductive Potential

Newly added information:

Based on animal data, KESIMPTA may cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)].

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17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Pregnancy

Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1, 8.3)].

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08/18/2025 (SUPPL-83)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.4 Liver Injury

Newly added subsection:

Clinically significant liver injury, without findings of viral hepatitis, has been reported in the postmarketing setting in patients treated with anti-CD20 B-cell depleting therapies approved for the treatment of MS, including KESIMPTA. Signs of liver injury, including markedly elevated serum hepatic enzymes with elevated total bilirubin, have occurred weeks to months after administration.

Patients treated with KESIMPTA found to have an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3x the upper limit of normal (ULN) with serum total bilirubin greater than 2x ULN, are potentially at risk for severe drug-induced liver injury.

Obtain liver function tests prior to initiating treatment with KESIMPTA [see Dosage and Administration (2.1)], and monitor for signs and symptoms of any hepatic injury during treatment. Measure serum aminotransferases, alkaline phosphatase, and bilirubin levels promptly in patients who report symptoms that may indicate liver injury, including new or worsening fatigue, anorexia, nausea, vomiting, right upper abdominal discomfort, dark urine, or jaundice. If liver injury is present and an alternative etiology is not identified, discontinue KESIMPTA.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

• Liver Injury [see Warnings and Precautions (5.4)]

  6.3 Postmarketing Experience

  Additions and/or revisions underlined:

  …

  Hepatobiliary Disorders: Liver injury [see Warnings and Precautions (5.4)]

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

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Liver Injury

Inform patients that liver injury has been reported with anti-CD20 B-cell depleting therapies, including KESIMPTA. Instruct patients treated with KESIMPTA to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, nausea, vomiting, right upper abdominal discomfort, dark urine, or jaundice. A blood test should be obtained before patients start therapy, and during treatment as clinically indicated [see Warnings and Precautions (5.4)].

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MEDICATION GUIDE

Additions and/or revisions underlined:

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Before using KESIMPTA, tell your healthcare provider about all of your medical conditions, including if you:

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• have a history of liver problems.

  …

  What are the possible side effects of KESIMPTA?

  KESIMPTA may cause serious side effects, including:

  …

• Liver damage. KESIMPTA may cause liver damage. Your healthcare provider will do blood tests to check your liver before you start KESIMPTA and while you take KESIMPTA if needed. Tell your healthcare provider right away if you have any symptoms of liver damage, such as:

  • yellowing of the skin and eyes (jaundice)

  • nausea

  • vomiting

  • unusual darkening of the urine

  • feeling tired or weak

    …

04/12/2024 (SUPPL-79)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

KESIMPTA is contraindicated in patients with:

• Active HBV infection [see Warnings and Precautions (5.1)].
• History of hypersensitivity to ofatumumab or life-threatening injection-related reaction to KESIMPTA. Hypersensitivity reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.2)].

5 Warnings and Precautions

5.2 Injection-Related Reactions and Hypersensitivity Reactions

Subsection title revised

Additions and/or revisions underlined:

KESIMPTA can result in systemic injection-related reactions and hypersensitivity reactions, which may be serious or life- threatening.

In Study 1 and Study 2, systemic and local injection reactions were reported in 21% and 11% of patients treated with KESIMPTA, compared to 15% and 6% of patients treated with teriflunomide who received matching placebo injections, respectively [see Adverse Reactions (6.1) and Clinical Studies (14)].

Injection-related reactions with systemic symptoms observed in clinical studies occurred most commonly within 24 hours of the first injection, but were also observed with later injections. Symptoms observed included fever, headache, myalgia, chills, and fatigue, and were predominantly (99.8%) mild to moderate in severity. There were no life-threatening injection reactions in the RMS clinical studies.

In the post-marketing setting, additional systemic injection-related reactions and hypersensitivity reactions have been reported, including anaphylaxis, angioedema, pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, dizziness, nausea, and tachycardia. Most cases were non-serious and occurred with the first injection. Most serious cases resulted in permanent discontinuation of KESIMPTA.

Symptoms of systemic injection-related reactions may be clinically indistinguishable from acute hypersensitivity reactions. A hypersensitivity reaction may occur with any injection. New or more severe symptoms compared to those experienced with previous injections should prompt consideration of a potential hypersensitivity reaction.

Only limited benefit of premedication with corticosteroids, antihistamines, or acetaminophen was observed in RMS clinical studies. The first injection of KESIMPTA should be performed under the guidance of an appropriately trained healthcare professional. If systemic injection-related reactions occur, initiate appropriate therapy. Patients who experience symptoms of systemic injection-related reactions or hypersensitivity reactions with KESIMPTA should be instructed to seek immediate medical attention.

If a hypersensitivity reaction or life-threatening systemic injection-related reaction occurs, immediately and permanently discontinue KESIMPTA [see Contraindications (4)]. If restarting KESIMPTA after a severe (but not life-threatening) systemic injection-related reaction or other event after which rechallenge is considered appropriate, administer the next KESIMPTA injection under clinical observation. If a mild to moderate injection-related reaction occurs, consider rechallenge under clinical observation.

Local injection-site reaction symptoms observed in clinical studies included erythema, swelling, itching, and pain. If local injection-related reactions occur, symptomatic treatment is recommended.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

The following clinically significant adverse reactions are discussed in greater detail elsewhere in the labeling:

• Infections [see Warnings and Precautions (5.1)]
• Injection-Related Reactions and Hypersensitivity Reactions [see Warnings and Precautions (5.2)]
• Reduction in Immunoglobulins [see Warnings and Precautions (5.3)]

6.3 Postmarketing Experience

Newly added subsection
Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to KESIMPTA during pregnancy. Healthcare providers are encouraged to enroll pregnant patients, or pregnant women may register themselves in the MotherToBaby Pregnancy Study in Multiple Sclerosis by calling 1-877-311-8972, by sending an email to MotherToBaby@health.ucsd.edu, or by going to www.mothertobaby.org/join-study.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Do not use KESIMPTA if you:

• have an active hepatitis B virus infection.
• have had an allergic reaction to ofatumumab or life-threatening injection-related reaction to KESIMPTA. See the end of this Medication Guide for a complete list of ingredients in KESIMPTA.

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Before using KESIMPTA, tell your healthcare provider about all of your medical conditions, including if you:

…

• are pregnant, think that you might be pregnant, or plan to become pregnant. It is not known if KESIMPTA will harm your unborn baby. Females who can become pregnant should use birth control (contraception) during treatment with KESIMPTA and for 6 months after your last treatment. Talk with your healthcare provider about what birth control method is right for you during this time.
  • Pregnancy Registry: There is a registry for women who become pregnant during treatment with KESIMPTA. If you become pregnant while taking KESIMPTA, tell your healthcare provider right away. Talk to your healthcare provider about registering with the MotherToBaby Pregnancy Study in Multiple Sclerosis. The purpose of the registry is to collect information about your health and your baby’s health. For more information or to register, contact MotherToBaby by calling 1-877-311-8972, by sending an email to MotherToBaby@health.ucsd.edu, or go to www.mothertobaby.org/join-study.

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What are the possible side effects of KESIMPTA? KESIMPTA may cause serious side effects, including:

See “What is the most important information I should know about KESIMPTA?”

• Injection-related reactions. Injection-related reactions are a common side effect of KESIMPTA. Injecting KESIMPTA can cause injection-related reactions that can happen within 24 hours (1 day) following the first injection and with later injections. There are two kinds of reactions:
• at or near the injection site: redness of the skin, swelling, itching and pain. Talk with your healthcare provider if you have any of these signs and symptoms.
• that may happen when certain substances are released in your body: fever, headache, pain in the muscles, chills, tiredness, rash, hives, trouble breathing, swelling of the face, eyelids, lips, mouth, tongue and throat, and feeling faint, or chest tightness. Contact your healthcare provider right away if you experience any of these signs and symptoms, especially if they become worse or you have new severe signs of reactions after subsequent injections. It could be a sign of an allergic reaction, which can be serious.

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PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Injection-Related Reactions and Hypersensitivity Reactions

Inform patients about the signs and symptoms of injection-related reactions and hypersensitivity reactions. Inform patients that injection-related reactions generally occur within 24 hours and predominantly following the first injection. A hypersensitivity reaction may occur with any injection, and any new or worsening symptoms with subsequent KESIMPTA injections should prompt consideration of a hypersensitivity reaction. Advise patients to seek immediate medical attention if they experience signs or symptoms of a severe or life-threatening injection-related reaction or hypersensitivity reaction, and to contact their healthcare provider if they experience any signs or symptoms of a injection- related reaction or hypersensitivity reaction [see Warnings and Precautions (5.2)].

Contraception

Advise females of childbearing potential to use effective contraception while receiving KESIMPTA and for 6 months after the last treatment of KESIMPTA [see Warnings and Precautions (5.4) and Use in Specific Populations (8.3)].

Pregnancy Exposure Registry

Instruct patients that if they are pregnant or plan to become pregnant while taking KESIMPTA, they should inform their healthcare provider. Encourage patients to enroll in the MotherToBaby Pregnancy Study in Multiple Sclerosis if they become pregnant while taking KESIMPTA [see Use in Specific Populations (8.1)].

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01/19/2024 (SUPPL-80)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Infections

(Additions and/or revisions underlined)

Serious, including life-threatening or fatal, bacterial, fungal, and new or reactivated viral infections have been observed during and following completion of treatment with anti-CD20 B-cell depleting therapies.

In KESIMPTA Study 1 and Study 2 [see Clinical Studies (14)], the overall rate of infections and serious infections in patients treated with KESIMPTA was similar to patients who were treated with teriflunomide (51.6% vs 52.7%, and 2.5% vs 1.8%, respectively). The most common infections reported by KESIMPTA-treated patients in the randomized clinical 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 the infection is resolved.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE KESIMPTA® (KEY-simp-ta) (ofatumumab) injection, for subcutaneous use

(Additions and/or revisions underlined)

What is the most important information I should know about KESIMPTA? KESIMPTA can cause serious side effects, including:

Infections. Serious infections, which can be life-threatening or cause death, can happen during treatment with KESIMPTA. If you have an active infection, your healthcare provider should delay your treatment with KESIMPTA until your infection is gone. KESIMPTA taken before or after other medicines that weaken the immune system may increase your risk of getting infections.

09/02/2022 (SUPPL-75)

Approved Drug Label (PDF)

Boxed Warning

Medication Guide

Additions and revisions underlined:

How should I store KESIMPTA?

• If needed, KESIMPTA may be stored for up to 7 days at room temperature, up to 86°F (30°C ).

• Write the date taken out of the refrigerator in the space provided on the carton.

• If stored below 86°F (30°C), unused KESIMPTA may be returned to the refrigerator and must be used within the next 7 days. If this KESIMPTA is not used within those 7 days, then discard the medicine.

08/20/2020 (SUPPL-70)

Approved Drug Label (PDF)

Other

Ofatumumab, a fully human type 1 IgG1 monoclonal antibody targeting CD20+ B cells, was originally approved on October 26, 2009, under the tradename (Arzerra), for the treatment of chronic lymphocytic leukemia (CLL) as an intravenous infusion.

This supplement introduces a new indication for ofatumumab for relapsing forms of multiple sclerosis (RMS). The labeling for the RMS indication is under the tradename KESIMPTA as a subcutaneous injection. Both KESIMPTA and ARZERRA share the same BLA number, but their labeling is different.

To view the KESIMPTA information, please refer to its labeling in its entirety.