Nipocalimab

1 INDICATIONS AND USAGE IMAAVY is indicated for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. IMAAVY is a neonatal Fc receptor blocker indicated for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. ( 1 )

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for instructions on dosage, preparation, and administration. ( 2.1 , 2.2 , 2.3 ) Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of IMAAVY. ( 2.1 ) Administer via intravenous infusion only. ( 2.2 ) The recommended initial dosage is 30 mg/kg once via intravenous infusion over at least 30 minutes. Two weeks after the initial dosage, administer a maintenance dosage of 15 mg/kg via intravenous infusion over at least 15 minutes, and continue every two weeks thereafter. ( 2.2 ) Must be diluted with 0.9% sodium chloride injection prior to administration. ( 2.3 ) Administer as an intravenous infusion via a 0.2 micron in-line or add-on filter. ( 2.3 ) 2.1 Recommended Vaccination Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of IMAAVY. Because IMAAVY causes transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with IMAAVY [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage Dilute IMAAVY prior to administration. Administer via intravenous infusion only [see Dosage and Administration (2.3) ] . The recommended initial dosage of IMAAVY is 30 mg/kg administered once via intravenous infusion over at least 30 minutes. Two weeks after the initial dosage administer a maintenance dosage of 15 mg/kg via intravenous infusion over at least 15 minutes. Continue the maintenance dosage every two weeks thereafter. If a scheduled infusion appointment is missed, the maintenance dosage of IMAAVY should be administered as soon as possible. Resume dosing every two weeks thereafter. 2.3 Preparation and Administration Instructions Prior to administration, dilute IMAAVY single-dose vials with only 0.9% sodium chloride injection using the instructions below. For patients who weigh 40 kg or more, the total volume to be administered is 250 mL; for patients who are 12 years or older and weigh less than 40 kg, the total volume to be administered is 100 mL (see Preparation ) . Preparation Prepare the solution for infusion using aseptic technique as follows: Calculate the dosage (mg), total drug volume (mL) of IMAAVY solution required, and the number of IMAAVY vials needed, based on the patient's current weight [see Dosage and Administration (2.2) ] . Each single-dose vial of IMAAVY is at a concentration of 185 mg/mL. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Check that the solution in each vial is colorless to slightly brownish, clear to slightly opalescent, and free of visible particles. Do not use if visible particles are present or if the solution is discolored (other than colorless to slightly brownish). Gently withdraw the calculated volume of IMAAVY from the vial(s). Discard any unused portion of the vials. Dilute total volume withdrawn of IMAAVY by adding to an infusion container containing 0.9% sodium chloride injection to a final volume of: 250 mL for patients who weigh 40 kg or more, or 100 mL for patients who weigh less than 40 kg. Only use infusion containers made of polyolefin, polypropylene, or polyvinylchloride. Gently invert the infusion container at least 10 times to mix the solution. Do not shake. Verify that a uniform solution has been achieved by visual inspection. Do not use if particulate matter or discoloration is present. Storage Conditions of the Diluted Solution Administer the diluted IMAAVY solution immediately after preparation. If the diluted IMAAVY solution is not used immediately: Protect from light. Store refrigerated at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. Do not freeze. After preparation or removal from the refrigerator, use or discard the IMAAVY diluted solution within 12 hours, including infusion time. During these 12 hours, store under ambient light at 15°C to 30°C (59°F to 86°F). Administration If the diluted solution is refrigerated prior to administration, allow to warm to room temperature. Do not use external heat sources to warm IMAAVY. Administer the diluted solution by intravenous infusion only using an infusion set with an in-line or add-on, sterile, non-pyrogenic, low protein-binding filter made of polyethersulfone or polysulfone (pore size 0.2 micrometer or less). Administration sets must be made of either polybutadiene, polyethylene, polyurethane, polypropylene, or polyvinylchloride. Do not infuse IMAAVY concomitantly in the same intravenous line with other agents. Administer IMAAVY infusion intravenously over at least 30 minutes for the initial dose (30 mg/kg) and at least 15 minutes for subsequent doses (15 mg/kg). If an adverse reaction occurs during administration of IMAAVY, the infusion may be slowed or stopped at the discretion of the healthcare professional. Monitor the patient for 30 minutes after each infusion for signs or symptoms of an infusion-related or hypersensitivity reaction [see Warnings and Precautions (5.2 , 5.3) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling Infections [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Infusion-related Reactions [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥10%) in patients with gMG treated with IMAAVY were respiratory tract infections, peripheral edema, and muscle spasms. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 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 practice. Adults In Study 1 and its extension study the safety of IMAAVY was evaluated in 186 patients with gMG who received at least one dose of IMAAVY. Of those patients, 168 patients were exposed to IMAAVY every 2 weeks for at least 6 months, and 140 patients were exposed for at least 12 months. In Study 1, 98 adult patients with gMG received IMAAVY 15 mg/kg every two weeks (after 30 mg/kg initial dose) [see Clinical Studies (14) ]. Of these 98 patients, approximately 67% were female, 67% were White, 29% were Asian, and 10% were of Hispanic or Latino ethnicity. The mean age at study entry was 53 years (range 20 to 81). Adverse reactions reported in at least 5% of patients treated with IMAAVY and more frequently than placebo, are summarized in Table 1. The most common adverse reactions (reported in at least 10% of patients treated with IMAAVY) were respiratory tract infection, peripheral edema, and muscle spasms. Table 1: Adverse Reactions (≥ 5%) of Patients Treated with IMAAVY and More Frequently than in Placebo in Study 1 Adverse Reaction IMAAVY N=98 % Placebo N=98 % Includes the following reported in patients treated with IMAAVY: Infection Respiratory tract infection COVID-19 (and other related terms), pneumonia, bronchitis, pneumonia bacteria 18 13 Urinary tract infection other related terms 6 3 Herpes zoster and Herpes simplex 6 2 Oral infection glossitis, oral candidiasis, pericoronitis, pulpitis dental, tooth abscess, tooth infection 5 3 Peripheral edema 12 2 Muscle spasm 12 3 Hypersensitivity reaction angioedema, dermatitis atopic, eczema, gingival swelling, rash (and other related terms), urticaria 8 7 Abdominal pain 8 3 Back pain 8 5 Pyrexia 7 1 Diarrhea 7 3 Cough 7 3 Anemia 6 4 Dizziness 5 1 Nausea 5 2 Hypertension 5 2 Insomnia 5 2 Infections In Study 1 and its extension study, infections that occurred in patients treated with IMAAVY (n=186) included upper respiratory tract infection (46%), respiratory tract infection (28%; including pneumonia, bronchitis, COVID-19), urinary tract infection (15%), herpes (8%; including herpes simplex, herpes zoster, herpes zoster oticus), influenza (8%), oral infection (8%; including candidiasis and dental infections), and skin infection (7%; including cellulitis). Two (1%) cases of infections (cellulitis and urinary tract infection) led to discontinuation of IMAAVY [see Warnings and Precautions (5.1) ] . Hypersensitivity Reactions In Study 1 and its extension study, out of 186 patients treated with IMAAVY, 30 (16%) patients experienced hypersensitivity reactions, which occurred within one hour to two weeks of administration. One patient experienced hypersensitivity reaction (urticaria) that required discontinuation of IMAAVY [see Warnings and Precautions (5.2) ] . Infusion-Related Reactions In Study 1 and its extension study, out of 186 patients treated with IMAAVY, 20 (11%) patients experienced infusion-related reactions, which occurred within one hour to 2 days of administration. No patients experienced infusion-related reaction that required discontinuation of IMAAVY [see Warnings and Precautions (5.3) ] . Laboratory Findings Lipids In Study 1 (N=98), patients treated with IMAAVY had elevations from normal to high of fasting total cholesterol ( ≥ 240 mg/dL) and LDL cholesterol ( ≥ 160 mg/dL) (24% and 11% of patients, respectively). In Study 1, these changes from baseline peaked at Week 4, then decreased and plateaued by Week 24 to mean increases of 14 mg/dL and 7 mg/dL, respectively. Five percent of patients treated with IMAAVY had decreases from normal to low (<40 mg/dL of fasting HDL cholesterol). Pediatric Patients 12 Years of Age and Older In a 24-week, single arm study evaluating the safety of IMAAVY in 7 pediatric patients age 12 to 16 years with gMG who were AChR positive, adverse reactions were consistent with those observed in adult patients with gMG [see Use in Specific Populations (8.4) ] .

12.3 Pharmacokinetics Nipocalimab exhibits nonlinear pharmacokinetics. Following a single intravenous infusion of IMAAVY at doses ranging from 0.3 to 60 mg/kg (4 times the recommended maintenance dosage) in healthy participants, C max of nipocalimab-aahu increased in a dose-proportional manner while AUC increased in a greater than dose-proportional manner. Distribution Mean volume of distribution of nipocalimab is 2.67 L. Metabolism Nipocalimab is expected to be degraded by proteolytic enzymes into small peptides and amino acids. Elimination Nipocalimab exhibits concentration-dependent pharmacokinetics. After a single intravenous administration of 15 mg/kg nipocalimab-aahu, the mean clearance is 0.0627 L/h and half-life is 29.3 hours. Specific Populations Age, Sex, and Race The pharmacokinetics of nipocalimab were not affected by age, sex, or race based on a population pharmacokinetics analysis. Pediatric Patients Following the recommended intravenous doses of IMAAVY in adolescent patients 12 to 16 years of age with gMG (N=7), the observed steady-state serum nipocalimab-aahu concentrations were within the range of those observed for adult patients with gMG [see Use in Specific Populations (8.4) ] . Patients with Renal Impairment No dedicated pharmacokinetic study has been conducted in patients with renal impairment. Renal impairment is not expected to affect the pharmacokinetics of nipocalimab. Based on a population pharmacokinetic analysis, which included healthy volunteers and patients with gMG with mild to moderate renal impairment, renal function (estimated glomerular filtration rate [eGFR] 30–89 mL/min/1.73 m 2 ) had no clinically significant effect on nipocalimab-aahu clearance. No dose adjustment is required in patients with renal impairment. Patients with Hepatic Impairment No dedicated pharmacokinetic study has been performed in patients with hepatic impairment. Nipocalimab is not metabolized by cytochrome P450 enzymes, and hepatic impairment is not expected to affect the pharmacokinetics of nipocalimab. Based on a population pharmacokinetic analysis, which included healthy volunteers and patients with gMG with mild to moderate hepatic impairment, there was no clinically significant effect on nipocalimab-aahu clearance. No dose adjustment is required in patients with hepatic impairment. Drug Interactions with Other Drugs or Biological Products IgG-Based Monoclonal Antibodies Nipocalimab decreases concentrations of compounds that bind to the human FcRn, including IgG based monoclonal antibodies. Cytochrome P450 Enzymes Nipocalimab is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.