Introduction

Pozelimab-bbfg, a recombinant monoclonal immunoglobulin G4 (IgG4) antibody, is a complement inhibitor.

Uses for Pozelimab (Systemic)

Pozelimab-bbfg has the following uses:

Pozelimab-bbfg is indicated for the treatment of adult and pediatric patients 1 year of age and older with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease.

Pozelimab (Systemic) Dosage and Administration

General

Pozelimab-bbfg is available in the following dosage form(s) and strength(s):

Injection: 400 mg/2 mL (200 mg/mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

See full prescribing information for meningococcal vaccine and prophylaxis recommendations prior to the first dose of pozelimab-bbfg.

Loading dose is administered by IV infusion; maintenance doses are administered by subcutaneous injection.

Pozelimab-bbfg for IV use:must be prepared and administered by a healthcare provider. Dilution is required prior to administration. Infuse through an IV line containing a sterile, in-line or add on 0.2-micron to 5-micron filter. Infuse over a minimum of 1 hour; do not exceed maximum rate of 1000 mg/hour. Observe the patient for 30 minutes following completion of the infusion.

Pozelimab-bbfg for subcutaneous use:must be prepared and administered by a healthcare provider. Withdraw appropriate dose volume and inject into the abdomen, thigh, or upper arm. Rotate sites. Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Observe the patient for 30 minutes following completion of the first subcutaneous injection.

See full prescribing information for instructions on preparation and administration.

Pediatric Patients

Dosage Recommendations

• Day 1 (loading dose): Administer a single 30 mg/kg dose by IV infusion after dilution.

• Day 8 and thereafter (maintenance dosage): Inject 10 mg/kg as a subcutaneous injection once weekly starting on Day 8.

• The maintenance dosage may be increased to 12 mg/kg once weekly if there is inadequate clinical response after at least 3 weekly doses (i.e., starting from Week 4).

• The maximum maintenance dosage is 800 mg once weekly by subcutaneous injection.

• Doses greater than 400 mg require 2 injections.

Adults

Dosage Recommendations

• Day 1 (loading dose): Administer a single 30 mg/kg dose by IV infusion after dilution.

• Day 8 and thereafter (maintenance dosage): Inject 10 mg/kg as a subcutaneous injection once weekly starting on Day 8.

• The maintenance dosage may be increased to 12 mg/kg once weekly if there is inadequate clinical response after at least 3 weekly doses (i.e., starting from Week 4).

• The maximum maintenance dosage is 800 mg once weekly by subcutaneous injection.

• Doses greater than 400 mg require 2 injections.

Contraindications

Pozelimab-bbfg is contraindicated in patients with unresolved Neisseria meningitidis infection.

Warnings/Precautions

Serious Meningococcal Infections

Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The use of pozelimab-bbfg increases a patient's susceptibility to serious and life-threatening meningococcal infections (septicemia and/or meningitis) caused by any serogroup, including nongroupable strains.

Complete or update meningococcal vaccination (for serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) at least 2 weeks prior to administering the first dose of pozelimab-bbfg, according to the most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of pozelimab-bbfg therapy.

If urgent pozelimab-bbfg therapy is indicated in a patient who is not up-to-date with both MenACWY and MenB vaccines according to ACIP recommendations, administer meningococcal vaccine(s) as soon as possible and provide the patient with antibacterial drug prophylaxis. The efficacy, duration, and drug regimens for antibacterial drug prophylaxis have not been studied in patients receiving complement inhibitors.

Because of inhibition of complement activity by pozelimab-bbfg, as well as risk of infection caused by nongroupable strains of N. meningitidis, vaccination does not eliminate the risk of meningococcal infections, despite development of antibodies following vaccination.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients and caregivers of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Interrupt treatment with pozelimab-bbfg in patients who are undergoing treatment for serious meningococcal infection until the infection is resolved.

Other Bacterial Infections

Pozelimab-bbfg blocks terminal complement activation; therefore, patients may have increased susceptibility to encapsulated bacterial infections, especially infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Patients treated with pozelimab-bbfg may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzaeType b (Hib) infections according to ACIP guidelines. Patients receiving pozelimab-bbfg are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination. Interrupt treatment with pozelimab-bbfg in patients who are undergoing treatment for a serious encapsulated bacterial infection until the infection is resolved. Counsel patients about gonorrhea prevention and advise regular testing for patients at risk.

Systemic Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported with administration of complement inhibitors. Interrupt pozelimab-bbfg and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Immune Complex Formation

Immune complex formation has been reported during the transition of therapy between complement inhibitors, resulting in transient decrease in drug concentrations as well as symptoms suggestive of hypersensitivity reactions. However, this has not been studied in patients with CD55-deficient protein-losing enteropathy (PLE) switching from other complement inhibitors to pozelimab. The potential for immune complex formation should be considered if switching complement inhibitors.

Specific Populations

Pregnancy

Although there are no data on pozelimab-bbfg use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, monoclonal antibodies can be actively transported across the placenta.

In an animal reproduction study in monkeys, pozelimab-bbfg did not adversely affect embryofetal or postnatal development when administered from pregnancy confirmation through parturition at doses that produced exposure up to 3.3 to 3.8 times the predicted clinical exposures (on an AUC basis).

The estimated 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 outcome. 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.

In an enhanced pre- and postnatal development study, pregnant female monkeys were subcutaneously administered pozelimab-bbfg at doses of 5 or 50 mg/kg once weekly from confirmation of pregnancy (gestation day 20) through parturition (approximately gestation day 160). No adverse effects were observed on maintenance of pregnancy, pregnancy outcome, or on the development of offspring through postnatal day 90 at doses up to 3.3-3.8 times the predicted clinical exposures.

Lactation

There are no data on the presence of pozelimab-bbfg in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Endogenous maternal IgG and monoclonal antibodies are transferred into human milk. The effects of local GI exposure and the extent of systemic exposure in the breastfed infant to pozelimab are unknown. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for pozelimab-bbfg and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of pozelimab-bbfg for the treatment of CD55-deficient protein-losing enteropathy (PLE) have been established in pediatric patients 1 year of age and older. Use of pozelimab-bbfg for this indication is supported by a single-arm study in 10 patients with active disease.

The safety and effectiveness of pozelimab-bbfg have not been established in pediatric patients less than 1 year of age.

Geriatric Use

CD55-deficient PLE is largely a disease of pediatric patients. Pozelimab-bbfg has not been studied in the geriatric population.

Common Adverse Effects

Most common adverse reactions (in 2 or more patients) are upper respiratory tract infection, fracture, urticaria, and alopecia.

General

Pozelimab-bbfg is available in the following dosage form(s) and strength(s):

Injection: 400 mg/2 mL (200 mg/mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

See full prescribing information for meningococcal vaccine and prophylaxis recommendations prior to the first dose of pozelimab-bbfg.

Loading dose is administered by IV infusion; maintenance doses are administered by subcutaneous injection.

Pozelimab-bbfg for IV use:must be prepared and administered by a healthcare provider. Dilution is required prior to administration. Infuse through an IV line containing a sterile, in-line or add on 0.2-micron to 5-micron filter. Infuse over a minimum of 1 hour; do not exceed maximum rate of 1000 mg/hour. Observe the patient for 30 minutes following completion of the infusion.

Pozelimab-bbfg for subcutaneous use:must be prepared and administered by a healthcare provider. Withdraw appropriate dose volume and inject into the abdomen, thigh, or upper arm. Rotate sites. Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Observe the patient for 30 minutes following completion of the first subcutaneous injection.

See full prescribing information for instructions on preparation and administration.

Pediatric Patients

Dosage Recommendations

• Day 1 (loading dose): Administer a single 30 mg/kg dose by IV infusion after dilution.

• Day 8 and thereafter (maintenance dosage): Inject 10 mg/kg as a subcutaneous injection once weekly starting on Day 8.

• The maintenance dosage may be increased to 12 mg/kg once weekly if there is inadequate clinical response after at least 3 weekly doses (i.e., starting from Week 4).

• The maximum maintenance dosage is 800 mg once weekly by subcutaneous injection.

• Doses greater than 400 mg require 2 injections.

Adults

Dosage Recommendations

• Day 1 (loading dose): Administer a single 30 mg/kg dose by IV infusion after dilution.

• Day 8 and thereafter (maintenance dosage): Inject 10 mg/kg as a subcutaneous injection once weekly starting on Day 8.

• The maintenance dosage may be increased to 12 mg/kg once weekly if there is inadequate clinical response after at least 3 weekly doses (i.e., starting from Week 4).

• The maximum maintenance dosage is 800 mg once weekly by subcutaneous injection.

• Doses greater than 400 mg require 2 injections.