Kesimpta

— THERAPEUTIC CATEGORIES —
  • Multiple sclerosis
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Kesimpta Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Ofatumumab 20mg/0.4mL; soln for SC inj; preservative-free.

    Pharmacological Class

    CD20-directed cytolytic monoclonal antibody.

    How Supplied

    Single-dose prefilled Sensoready pen—1; Single-dose prefilled syringe—1

    Storage

    Kesimpta Sensoready pens and prefilled syringes must be refrigerated at 2ºC to 8ºC (36ºF to 46ºF). Do not freeze.

    Keep the product in the original carton to protect from light until the time of use. 

    To avoid foaming, do not shake.

    If necessary, Kesimpta may be stored for up to 7 days at room temperature, not to exceed 30°C (86°F).

    If stored below 30°C (86°F), unused Kesimpta may be returned to the refrigerator and must be used within the next 7 days or discarded after 7 days.

     

    Manufacturer

    Novartis Pharmaceuticals Corp

    Generic Availability

    NO

    Mechanism of Action

    The precise mechanism by which ofatumumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ofatumumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.

    Kesimpta Indications

    Indications

    Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

    Kesimpta Dosage and Administration

    Prior to Treatment Evaluations

    Hepatitis B Virus (HBV) Screening

    • Perform HBV screening. 
    • Negative for HBsAg and positive for Hepatitis B core antibody [HBcAb+] or carriers of HBV [HBsAg+]: Consult liver disease experts before starting and during treatment.
    • Active HBV confirmed by positive results for Hepatitis B surface antigen [HBsAg] and anti-HBV tests: Contraindicated.

    Serum Immunoglobulins

    • Perform testing for quantitative serum immunoglobulins.
    • Low serum immunoglobulins: Consult immunology experts before initiating treatment.

    Vaccinations

    • Live-attenuated or live vaccines not recommended during treatment and after discontinuation until B-cell repletion.
    • Administer immunizations according to guidelines at least 4 weeks before initiation of Kesimpta for live or live-attenuated vaccines, and whenever possible, at least 2 weeks before starting treatment for inactivated vaccines.

    Adult

    Perform first inj under the guidance of a healthcare provider. Give by SC inj into abdomen, thigh, or outer upper arm. Initially 20mg at Weeks 0, 1, and 2, followed by 20mg once monthly starting at Week 4.

    Children

    Not established.

    Administration

    Administer by subcutaneous injection.

    First injection: Under the guidance of a health care professional.

    Subsequent injections: Patient self-administration.

    Administer in the abdomen, thigh, or outer upper arm subcutaneously. Do not give injections into moles, scars, stretch marks, or areas where the skin is tender, bruised, red, scarly, or hard.

    Kesimpta Sensoready pens and syringes: 

    • For one-time use only; discard after use
    • Before administration, remove from the refrigerator and allow to reach room temperature for about 15-30 minutes.
    • Do not remove the needle cover while allowing the prefilled syringe to reach room temperature.
    • Do not use if liquid contains visible particles or is cloudy.

    Missed dose: Administer as soon as possible without waiting until the next scheduled dose; subsequent doses should be administered at the recommended intervals.

    Kesimpta Contraindications

    Contraindications

    Active HBV infection.

    Kesimpta Boxed Warnings

    Not Applicable

    Kesimpta Warnings/Precautions

    Warnings/Precautions

    Increased risk of infections. Delay Kesimpta in those with active infection until resolved. Risk of HBV reactivation. Perform HBV screening in all patients prior to initiation. Withhold at first sign/symptom of progressive multifocal leukoencephalopathy (PML) and evaluate; discontinue if confirmed. Permanently discontinue if hypersensitivity reaction or life-threatening systemic inj-related reaction occurs; consider rechallenge under clinical observation if appropriate for mild to severe (not life-threatening) reactions. Monitor levels of quantitative serum immunoglobulins before initiating, during and after discontinuation until B-cell repletion; consider discontinuing if low immunoglobulins with a serious opportunistic infection or recurrent infections occur, or if prolonged hypogammaglobulinemia requires IV immunoglobulins. Complete all immunizations according to guidelines ≥4 weeks for live or live-attenuated vaccines, and if possible, ≥2 weeks for non-live vaccines prior to initiation. Infants born to mothers treated during pregnancy: do not administer live or live-attenuated vaccines before confirming B-cell recovery; non-live vaccines may be given prior to recovery, but should consider assessment of vaccine immune response. Advise females or reproductive potential to use effective contraception during and ≥6 months after the last dose. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Infections

    • Increased risk of infections seen with other anti-CD20 B-cell depleting therapies.
    • Upper respiratory tract infection and urinary tract infection most commonly reported in clinical trials with Kesimpta.
    • Delay treatment in patients with active infection until the infection resolves.
    • Increased immunosuppressive effects if Kesimpta is initiated after an immunosuppressive therapy or if an immunosuppressive therapy is initiated after Kesimpta.
    • HBV reactivation has been reported with ofatumumab for chronic lymphocytic leukemia (at higher IV doses but for a shorter duration of treatment) and in patients treated with other anti-CD20 antibodies.
    • Fatal infections caused by HBV in patients who have not been previously infected have occurred in patients being treated with ofatumumab for CLL.
    • Contraindicated with active hepatitis B disease; HBV screening should be performed before initiating treatment (See Prior to Treatment Evaluations).
    • Progressive multifocal leukoencephalopathy has occurred with ofatumumab for CLL; withhold Kesimpta and perform appropriate diagnostic tests if suspected (MRI findings may be apparent before clinical signs/symptoms). Discontinue treatment if PML is confirmed.

    Vaccinations

    • Live-attenuated or live vaccines not recommended during treatment and after discontinuation until B-cell repletion.
    • Kesimpta may interfere with the effectiveness of inactivated vaccines.
    • Administer immunizations according to guidelines at least 4 weeks before initiation of Kesimpta for live or live-attenuated vaccines, and whenever possible, at least 2 weeks before starting treatment for inactivated vaccines.
    • See Pediatric Considerations for vaccination of infants born to mothers treated with Kesimpta during pregnancy.

    Injection-Related Reactions and Hypersensitivity Reactions

    • Occurred most commonly within 24 hours of the first injection but were observed with later injections.
    • Symptoms: Fever, headache, myalgia, chills, fatigue.
    • Local reactions: Erythema, swelling, itching, pain.
    • Symptomatic treatment recommended if injection-related reactions occur.
    • Permanently discontinue if a hypersensitivity reaction or life-threatening systemic injection-related reaction occurs.
    • Consider rechallenge under clinical observation if restarting Kesimpta after a mild to moderate injection-related reaction or a severe (not life-threatening) systemic injection-related reaction occurs.

    Reduction in Immunoglobulins

    • Decreased immunoglobulin levels observed with B-cell depleting therapy.
    • Monitor levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy until B-cell repletion.
    • Serious opportunistic infection, recurrent infections or prolonged hypogammaglobulinemia requiring treatment with intravenous immunoglobulins in a patient with low immunoglobulins: consider discontinuing Kesimpta.

    Pregnancy Considerations

    Animal data: Ofatumumab may cross the placenta and cause fetal B-cell depletion. Kesimpta may 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.

     

    Nursing Mother Considerations

    No data on the presence of ofatumumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Consider the benefit to the mother vs the potential risk to the infant.

    Pediatric Considerations

    Safety and effectiveness in pediatric patients have not been established.

    Vaccination of Infants Born to Mothers Treated With Kesimpta During Pregnancy

    • Do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts. 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 recovery from B-cell depletion, 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.

    Geriatric Considerations

    Clinical studies did not include sufficient numbers of geriatric patients to determine whether they respond differently from younger patients.

    Other Considerations for Specific Populations

    Females of reproductive age: Use effective contraception while receiving Kesimpta and for at last 6 months after the last dose.

    Kesimpta Pharmacokinetics

    Absorption

    After subcutaneous administration, ofatumumab is believed to be predominantly absorbed via the lymphatic system.

    Metabolism

    Degradation to small peptides and amino acids by ubiquitous proteolytic enzymes.

    Elimination

    Ofatumumab is eliminated by both linear catabolic pathways and a non-linear B-cell mediated pathway. The half-life at steady state was estimated to be ~16 days following subcutaneous administration of repeated Kesimpta 20mg dosage.

    Kesimpta Interactions

    Interactions

    Concomitant live or live-attenuated vaccines: not recommended during treatment and after discontinuation until B-cell repletion. May interfere with the effectiveness of non-live vaccines. Potential additive immunosuppressive effects with other immunosuppressants including systemic corticosteroids.

    Kesimpta Adverse Reactions

    Adverse Reactions

    Upper respiratory tract infection, headache, inj-related reactions, local inj-site reactions; infections, reduction in immunoglobulins.

    Kesimpta Clinical Trials

    Clinical Trials

    The phase 3 ASCLEPIOS I (ClinicalTrials.gov Identifier: NCT02792218) and II (ClinicalTrials.gov Identifier: NCT02792231) trials compared the efficacy and safety of Kesimpta with teriflunomide, a pyrimidine synthesis inhibitor, in 1882 adult patients with relapsing forms of MS. 

    Patients were randomly assigned to receive Kesimpta 20mg subcutaneously on days 1, 7, and 14, followed by once monthly starting at week 4, or a daily oral placebo, or oral teriflunomide 14mg once daily. The primary end point of both studies was annualized relapse rate (ARR) in patients treated for up to 30 months.

    Results showed that Kesimpta significantly reduced ARR by 51% and 58% in ASCLEPIOS I and II when compared with teriflunomide (ARR=0.11 and 0.10 vs 0.22 and 0.25, P <.001), respectively. 

    Kesimpta  significantly reduced the risk of 3-month confirmed disability progression by 34.3% (P =.003) compared with teriflunomide.

    Kesimpta also significantly reduced the number of T1 GdE lesions (P <.001) and the rate of new or enlarging T2 lesions (P <.001) in both studies.

    Similar effects were observed in an exploratory subgroup analysis based on sex, age, body weight, prior non-steroid MD therapy, and baseline disability and disease activity.

    Kesimpta Note

    Not Applicable

    Kesimpta Patient Counseling

    Patient Counseling

    Instruct patients how to administer Kesimpta and on proper syringe and needle disposal. 

    Report signs/symptoms of infection.

    HBV reactivation possible and at-risk patients will need to be monitored.

    Symptoms associated with PML: Progressive weakness on 1 side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

    Vaccination during treatment: See Warnings and Precautions.

    Inform patients of injection-related reactions.

    Females of childbearing potential: Use effective contraception during treatment and for 6 months after the last treatment.

    Cost Savings Program

    Kesimpta Patient Support Services

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