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• Dilute total volume withdrawn of IMAAVY by adding to an infusion container containing 0.9% sodium chloride injection to a final volume of: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.

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)].

Latent Viral Infections

Patients treated with IMAAVY may be at an increased risk of activation of latent viral infections, such as herpes zoster [see Adverse Reactions (6.1)] . In the extension period of Study 1, there were 2 patients with serious adverse reactions related to Epstein-Barr virus (EBV) infection, and 1 of these patients had fatal complications. Patients who screened positive for hepatitis were excluded from Study 1. Follow standard vaccination guidelines [see Dosage and Administration (2.1)].

Immunization

The safety of immunization with live vaccines and the immune response to vaccination during treatment with IMAAVY are unknown. Because IMAAVY causes a reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with IMAAVY.

Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of treatment with IMAAVY.

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.

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

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)] .

Risk Summary

There are limited data on the use of IMAAVY in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

There was no evidence of direct adverse effects on fetal development following administration of nipocalimab-aahu to pregnant monkeys; however, adverse effects on the placenta were associated with fetal loss at both doses tested (see Data) .

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

There is a pregnancy safety study for IMAAVY. If IMAAVY is administered during pregnancy, or if a patient becomes pregnant while receiving IMAAVY, healthcare providers should report IMAAVY exposure by contacting Janssen at 1-800-526-7736 or www.IMAAVY.com

Clinical Considerations

Animal Data

Intravenous administration of nipocalimab-aahu (0, 100, or 300 mg/kg) to pregnant monkeys weekly from the end of organogenesis (gestation day 45) through parturition resulted in placental ischemia, associated with fetal loss and decreased levels of IgG in the offspring at both doses tested. IgG levels in offspring returned to normal levels and no adverse effects on immune function were evident by 6 months after birth. The doses tested are 6 and 20 times the recommended human maintenance dose (15 mg/kg) on a mg/kg basis.

Risk Summary

Nipocalimab-aahu is excreted in human colostrum and breastmilk based on limited data from an investigational study of 13 pregnant women administered nipocalimab-aahu during pregnancy where colostrum and breastmilk was assessed in the first 8 days after birth. There are insufficient data on the effect of IMAAVY in the breastfed infant. There are no data on the effect of nipocalimab on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for IMAAVY, and any potential adverse effects on the breastfed infant from IMAAVY, or from the underlying maternal condition.

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

Drug Interactions with Other Drugs or Biological Products

Carcinogenesis

Studies to assess the carcinogenic potential of nipocalimab-aahu have not been conducted.

Mutagenesis

Studies to assess the genotoxic potential of nipocalimab-aahu have not been conducted. As an antibody, nipocalimab-aahu is not expected to interact directly with DNA.

Impairment of Fertility

Once or twice weekly intravenous administration of nipocalimab-aahu (0, 20, 50, 100, or 300 mg/kg) to male and female monkeys for 26 weeks resulted in no adverse effects on reproductive organs upon histopathological examination. The highest dose tested was 20 times the recommended human maintenance dose (15 mg/kg) on a mg/kg basis.

Unopened Vials

Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until the time of use. Do not freeze. Do not shake.

Diluted Solution

For storage of the diluted IMAAVY solution, see Dosage and Administration (2.3).