Kesimpta (ofatumumab): Uses, Dosage, Side Effects & Warnings

Uses

1 INDICATIONS AND USAGE 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. 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. ( 1 )

Dosage and administration

Before initiating KESIMPTA, screen for Hepatitis B virus (HBV) and obtain serum quantitative immunoglobulins, aminotransferases, alkaline phosphatase, and bilirubin. ( 2.1 ) Administer KESIMPTA by subcutaneous injection only. ( 2.2 , 2.3 ) Initial Dosing: 20 mg administered at Weeks 0, 1, and 2. ( 2.2 ) Subsequent Dosing: 20 mg administered monthly starting at Week 4. ( 2.2 ) 2.1 Assessments Prior to First Dose of KESIMPTA 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 [see Warnings and Precautions (5.1)] . Serum Immunoglobulins Prior to initiating KESIMPTA, perform testing for quantitative serum immunoglobulins [see Warnings and Precautions (5.3)] . 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 [see Warnings and Precautions (5.1)] . Liver Function Tests Prior to initiating KESIMPTA, obtain serum aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase, and bilirubin levels [see Warnings and Precautions (5.4)] . 2.2 Recommended Dosage 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. 2.3 Administration Instructions Administer by subcutaneous injection only. KESIMPTA is intended for patient self-administration by subcutaneous injection. Administer KESIMPTA in the abdomen, thigh, or outer upper arm subcutaneously. Do not give injection into moles, scars, stretch marks, or areas where the skin is tender, bruised, red, scaly, or hard. The first injection of KESIMPTA should be performed under the guidance of a healthcare professional [see Warnings and Precautions (5.2)] . KESIMPTA Sensoready ® pens and syringes are for one-time use only and should be discarded after use. See Instructions for Use for complete administration instructions. 2.4 Preparation of KESIMPTA The KESIMPTA “Instructions for Use” for each presentation contains more detailed instructions on the preparation of KESIMPTA. Before administration, remove KESIMPTA Sensoready Pen or KESIMPTA prefilled syringe from the refrigerator and allow KESIMPTA to reach room temperature for about 15 to 30 minutes. DO NOT remove the needle cover while allowing the prefilled syringe to reach room temperature. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the liquid contains visible particles or is cloudy.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS KESIMPTA is a clear to slightly opalescent, and colorless to slightly brownish-yellow solution available as follows: Injection: 20 mg/0.4 mL in a single-dose prefilled Sensoready Pen Injection: 20 mg/0.4 mL in a single-dose prefilled syringe Injection: 20 mg/0.4 mL solution in a single-dose prefilled Sensoready ® Pen ( 3 ) Injection: 20 mg/0.4 mL solution in a single-dose prefilled syringe ( 3 )

Contraindications

4 CONTRAINDICATIONS 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)] . Active HBV infection. ( 4 ) History of hypersensitivity to ofatumumab or life-threatening injection-related reaction to KESIMPTA. ( 4 )

Warnings and precautions

Infections: Serious, including life-threatening and fatal infections, have occurred in patients treated with anti-CD20 therapies. Delay KESIMPTA administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with KESIMPTA and after discontinuation, until B-cell repletion. ( 5.1 ) Injection-Related Reactions and Hypersensitivity Reactions: Management for injection-related reactions and hypersensitivity reactions depends on the type and severity of the reaction. ( 4 , 5.2 ) Reduction in Immunoglobulins: Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with KESIMPTA until B-cell repletion. Consider discontinuing KESIMPTA if a patient develops a serious opportunistic infection or recurrent infections if immunoglobulin levels indicate immune compromise. ( 5.3 ) Liver Injury: Clinically significant liver injury has occurred. Obtain serum aminotransferases, alkaline phosphatase, and bilirubin levels before initiating KESIMPTA, and during treatment as clinically indicated. Discontinue KESIMPTA in patients with evidence of liver injury in the absence of an alternative etiology. ( 5.4 ) Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping KESIMPTA. ( 5.5 , 8.1 ) 5.1 Infections 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. Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants When initiating KESIMPTA after an immunosuppressive therapy or initiating an immunosuppressive therapy after KESIMPTA, consider the potential for increased immunosuppressive effects [see Drug Interactions (7.1) and Clinical Pharmacology (12.2)] . KESIMPTA has not been studied in combination with other MS therapies. Hepatitis B Virus Reactivation There were no reports of 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 being treated with ofatumumab for chronic lymphocytic leukemia (CLL) (at higher intravenous doses than the recommended dose in MS but for a shorter duration of treatment) 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 being treated with ofatumumab for CLL (at higher intravenous doses than the recommended dose in MS but for a shorter duration of treatment). HBV screening should be performed in all patients before initiation of treatment with KESIMPTA. At a minimum, screening should include Hepatitis B surface antigen (HBsAg) and Hepatitis B Core Antibody (HBcAb) testing. These can be complemented with other appropriate markers as per local guidelines. For patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment with KESIMPTA. These patients should be monitored and managed following local medical standards to prevent HBV infection or reactivation. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML have been reported for KESIMPTA in the RMS clinical studies, PML resulting in death has occurred in patients being treated with ofatumumab for CLL (at substantially higher intravenous doses than the recommended dose in MS but for a shorter duration of treatment). In addition, JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies. At the first sign or symptom suggestive of PML, withhold KESIMPTA and perform an appropriate diagnostic evaluation. Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. If PML is confirmed, treatment with KESIMPTA should be discontinued. Vaccinations 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. KESIMPTA may interfere with the effectiveness of inactivated vaccines. The safety of immunization with live or live-attenuated vaccines following KESIMPTA therapy has not been studied.

Side effects

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)] Liver Injury [see Warnings and Precautions (5.4)] Most common adverse reactions (incidence greater than 10%) are upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Approximately 1500 patients with RMS received KESIMPTA in clinical studies. In Study 1 and Study 2, 1882 patients with RMS were randomized, 946 of whom were treated with KESIMPTA for a median duration of 85 weeks; 33% of patients receiving KESIMPTA were treated for up to 120 weeks [see Clinical Studies (14.1)] . The most common adverse reactions occurring in greater than 10% of patients treated with KESIMPTA and more frequently than in patients treated with teriflunomide were upper respiratory tract infections, injection-related reactions (systemic), headache, and injection-site reactions (local). The most common cause of discontinuation in patients treated with KESIMPTA was low immunoglobulin M (3.3%), defined in trial protocols as IgM at 10% below the lower limit of normal (LLN). Table 1 summarizes the adverse drug reactions that occurred in Study 1 and Study 2. Table 1: Adverse Reactions in Patients With RMS With an Incidence of at Least 5% With KESIMPTA and a Greater Incidence Than Teriflunomide (Pooled Study 1 and Study 2) a Includes the following: nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, pharyngitis, rhinitis, viral upper respiratory infection, tonsillitis, acute sinusitis, pharyngotonsillitis, laryngitis, pharyngitis streptococcal, viral rhinitis, sinusitis bacterial, tonsillitis bacterial, viral pharyngitis, viral tonsillitis, chronic sinusitis, nasal herpes, tracheitis. Adverse reactions KESIMPTA 20 mg N = 946 % Teriflunomide 14 mg N = 936 % Upper respiratory tract infections a 39 38 Injection-related reactions (systemic) 21 15 Headache 13 12 Injection-site reactions (local) 11 6 Urinary tract infection 10 8 Back pain 8 6 Blood immunoglobulin M decreased 6 2 Injection-Related Reactions and Injection-Site Reactions The incidence of injection-related reactions (systemic) was highest with the first injection (14.4%), decreasing with subsequent injections (4.4% with second, less than 3% with third injection). Injection-related reactions were mostly (99.8%) mild to moderate in severity. Two (0.2%) patients treated with KESIMPTA reported serious injection-related reactions. There were no life-threatening injection-related reactions. Most frequently reported symptoms (2% or greater) included fever, headache, myalgia, chills, and fatigue. In addition to systemic injection-related reactions, local reactions at the administration site were very common. Local injection-site reactions were all mild to moderate in severity. The most frequently reported symptoms (2% or greater) included erythema, pain, itching, and swelling [see Warnings and Precautions (5.2)] . Laboratory Abnormalities Immunoglobulins In Study 1 and Study 2, a decrease in the mean level of IgM was observed in KESIMPTA-treated patients but was not associated with an increased risk of infections [see Warnings and Precautions (5.3)] . In 14.3% of patients in Study 1 and Study 2, treatment with KESIMPTA resulted in a decrease in a serum IgM that reached a value below 0.34 g/L. KESIMPTA was associated with a decrease of 4.3% in mean IgG levels after 48 weeks of treatment and an increase of 2.2% after 96 weeks. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medication, and the underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other ofatumumab products may be misleading. Treatment-induced anti-drug antibodies (ADAs) were detected in 2 of 914 (0.2%) KESIMPTA-treated patients; no patients with treatment-enhancing or neutralizing ADAs were identified. There was no impact of positive ADA titers on pharmacokinetics, safety profile or B-cell kinetics in any patient; however, these data are not adequate to assess the impact of ADAs on the safety and efficacy of KESIMPTA. 6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of KESIMPTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System: Hypersensitivity reactions [see Warnings and Precautions (5.2)] Hepatobiliary Disorders: Liver injury [see Warnings and Precautions (5.4)]

Drug interactions

7.1 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. When switching from therapies with immune effects, the duration and mechanism of action of these therapies should be taken into account because of potential additive immunosuppressive effects when initiating KESIMPTA.

Use in specific populations

8.1 Pregnancy 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. Risk Summary 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. 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 (C avg ) 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 (C avg ) 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 (C avg ) 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). 8.2 Lactation Risk Summary 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. 8.3 Females and Males of Reproductive Potential Based on animal data, KESIMPTA may cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)] . Contraception Females of childbearing potential should use effective contraception while receiving KESIMPTA and for 6 months after the last treatment of KESIMPTA. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of KESIMPTA did not include sufficient numbers of geriatric patients to determine whether they respond differently from younger subjects.

Pregnancy

8.1 Pregnancy 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. Risk Summary 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. 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 (C avg ) 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 (C avg ) 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 (C avg ) 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).

Pediatric use

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Clinical studies of KESIMPTA did not include sufficient numbers of geriatric patients to determine whether they respond differently from younger subjects.

Description

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.

Mechanism of action

12.1 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.

How supplied

16.1 How Supplied KESIMPTA (ofatumumab) injection is a preservative-free, clear to slightly opalescent and colorless to slightly brownish-yellow solution for subcutaneous administration, which is supplied as follows: KESIMPTA Sensoready Pen: Carton of one 20 mg/0.4 mL single-dose prefilled Sensoready Pen NDC 0078-1007-68 KESIMPTA Prefilled Syringe: Carton of one 20 mg/0.4 mL single-dose prefilled syringe NDC 0078-1007-69 16.2 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. If necessary, KESIMPTA may be stored for up to 7 days at room temperature, not to exceed 30°C (86°F). Write the date removed from the refrigerator in the space provided on the carton labeling. 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. 16.1 How Supplied KESIMPTA (ofatumumab) injection is a preservative-free, clear to slightly opalescent and colorless to slightly brownish-yellow solution for subcutaneous administration, which is supplied as follows: KESIMPTA Sensoready Pen: Carton of one 20 mg/0.4 mL single-dose prefilled Sensoready Pen NDC 0078-1007-68 KESIMPTA Prefilled Syringe: Carton of one 20 mg/0.4 mL single-dose prefilled syringe NDC 0078-1007-69

Storage

16.2 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. If necessary, KESIMPTA may be stored for up to 7 days at room temperature, not to exceed 30°C (86°F). Write the date removed from the refrigerator in the space provided on the carton labeling. 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.

Patient information

Advise the patient to read FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections Advise patients to contact their healthcare provider for any signs of infection during treatment or after the last dose. Signs include fever, chills, constant cough, or dysuria [see Warnings and Precautions (5.1)] . Advise patients that KESIMPTA may cause reactivation of hepatitis B infection and that monitoring will be required if they are at risk [see Warnings and Precautions (5.1)] . Advise patients that PML has happened with an intravenous form of ofatumumab administered at a higher intravenous dosage in patients with CLL, as well as with drugs that are similar to KESIMPTA, and may happen with KESIMPTA. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their healthcare provider if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes [see Warnings and Precautions (5.1)] . Vaccinations Advise patients to complete any required live or live-attenuated vaccinations at least 4 weeks and, whenever possible at least 2 weeks, prior to initiation of KESIMPTA for inactivated vaccines. Administration of live-attenuated or live vaccines is not recommended during KESIMPTA treatment and until B-cell recovery [see Warnings and Precautions (5.1)] . 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 an injection-related reaction or hypersensitivity reaction [see Warnings and Precautions (5.2)] . 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)] . 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 (5.5) and Use in Specific Populations (8.3)] . 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)] . 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)] . Instruction on Injection Technique Patients or caregivers should be instructed by a healthcare professional on how to administer KESIMPTA [see Instructions for Use] . Instruct patients or caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items. Instruct patients to inject the full amount of KESIMPTA according to the directions provided in the Instructions for Use. Dispose of pens and syringes in a puncture-resistant container. Manufactured by: Novartis Pharmaceuticals Corporation East Hanover, NJ 07936 U.S. License No.: 1244 KESIMPTA and SENSOREADY are [registered] trademarks of Novartis AG. T2026-07

Active ingredients

Ofatumumab in 1 product

Kesimpta NDC products (1)

NDC	Strength & form	Labeler	Type
0078-1007	Ofatumumab 20 mg/.4mL Injection, Solution	Novartis Pharmaceuticals Corporation	BLA

Frequently asked questions

What is Kesimpta used for?

1 INDICATIONS AND USAGE 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. KESIMPTA is a CD20-directed cytolytic antibody indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome,…

What are the side effects of Kesimpta?

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)] Liver Injury [see Warnings and Precautions (5.4)] Most common adverse… See the full label for the complete list.

Who makes Kesimpta?

Kesimpta is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.