KESIMPTA® (ofatumumab) injection
Ofatumumab is a recombinant human monoclonal immunoglobulin G1 (IgG1) antibody that binds to human CD20 expressed on B-cells. Ofatumumab is produced in a murine NS0 cell line and consists of two IgG1 heavy chains and two kappa light chains with a molecular weight of approximately 146 kDa.
KESIMPTA (ofatumumab) injection is a sterile, preservative-free solution for subcutaneous use.
Each 20 mg/0.4 mL KESIMPTA Sensoready pen or prefilled syringe delivers 0.4 mL of solution. Each 0.4 mL contains 20 mg of ofatumumab, and arginine (4 mg), disodium edetate (0.007 mg), polysorbate 80 (0.08 mg), sodium acetate trihydrate (2.722 mg), sodium chloride (1.192 mg), and Water for Injection, USP with a pH of 5.5. Hydrochloric acid may have been added to adjust pH.
Indications and usage
KESIMPTA is a CD20-directed cytolytic antibody 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
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.
Dosage and administration
Hepatitis B Virus Screening: Prior to initiating KESIMPTA, perform Hepatitis B virus (HBV) screening. KESIMPTA is contraindicated in patients with active HBV confirmed by positive results for Hepatitis B surface antigen [HBsAg] and anti-HBV tests. For patients who are negative for HBsAg and positive for Hepatitis B core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment with KESIMPTA
Serum Immunoglobulins: Prior to initiating KESIMPTA, perform testing for quantitative serum immunoglobulins. For patients with low serum immunoglobulins, consult immunology experts before initiating treatment with KESIMPTA.
Vaccinations: Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of KESIMPTA for live or live-attenuated vaccines, and whenever possible, at least 2 weeks prior to initiation of KESIMPTA for inactivated vaccines
The recommended dosage of KESIMPTA is:
- initial dosing of 20 mg by subcutaneous injection at Weeks 0, 1, and 2, followed by
- subsequent dosing of 20 mg by subcutaneous injection once monthly starting at Week 4.
Missed Doses: If an injection of KESIMPTA is missed, it should be administered as soon as possible without waiting until the next scheduled dose. Subsequent doses should be administered at the recommended intervals.
KESIMPTA is contraindicated in patients with active HBV infection
Most common adverse reactions (incidence greater than 10%) are upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions.
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 of these infections have been fatal in patients treated with other anti-CD20 antibodies.
Injection-Related Reactions: 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.
Local injection-site reaction symptoms observed in clinical studies included erythema, swelling, itching, and pain.
Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 7.7% of patients treated with KESIMPTA compared to 3.1% of patients treated with teriflunomide in RMS clinical trials. Treatment was discontinued because of decreased immunoglobulins in 3.4% of patients treated with KESIMPTA and in 0.8% of patients treated with teriflunomide. No decline in immunoglobulin G (IgG) was observed at the end of the study.
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
Immunosuppressive or Immune-Modulating Therapies: Concomitant usage of KESIMPTA with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with KESIMPTA.
Use in specific populations
Pregnancy: There are no adequate data on the developmental risk associated with the use of KESIMPTA in pregnant women. Ofatumumab may cross the placenta and cause fetal B-cell depletion based on findings from animal studies
Transient peripheral B-cell depletion and lymphocytopenia have been reported 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 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 until B-cell recovery occurs
Lactation: There are 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. Human IgG is excreted in human milk, and the potential for absorption of ofatumumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for KESIMPTA and any potential adverse effects on the breastfed infant from KESIMPTA or from the underlying maternal condition.
Contraception: Females of childbearing potential should use effective contraception while receiving KESIMPTA and for 6 months after the last treatment of KESIMPTA
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Geriatric Use: Clinical studies of KESIMPTA did not include sufficient numbers of geriatric patients to determine whether they respond differently from younger subjects.
Storage and Handling
KESIMPTA Sensoready pens and prefilled syringes must be refrigerated at 2ºC to 8ºC (36ºF to 46ºF). Keep the product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming, do not shake.