Pozelimab-bbfg (Monograph)

Brand name: Veopoz
Drug class: Complement Inhibitors

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Warning

Life-threatening and fatal meningococcal infections reported in patients treated with complement inhibitors; such infections can become rapidly life-threatening or fatal if not recognized and treated early.
Complete or update meningococcal vaccinations ≥2 weeks prior to administering first dose of pozelimab-bbfg, unless risks of delaying therapy outweigh those of developing meningococcal infection. Follow the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor.
Patients receiving pozelimab-bbfg at increased risk for invasive disease due to Neisseria meningitidis, even if they develop antibodies following vaccination.
Monitor patients for early signs of meningococcal infections; evaluate immediately if infection suspected.

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Introduction

Terminal complement inhibitor; a human immunoglobulin IgG₄ recombinant monoclonal antibody.

Uses for Pozelimab-bbfg

CD55-deficient Protein-losing Enteropathy

Treatment of CD55-deficient protein-losing enteropathy, also known as complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE) disease, in adults and pediatric patients ≥1 year of age (designated an orphan drug by FDA for this use).

Complement inhibitor therapies (e.g., eculizumab) have been tested for clinical efficacy in treatment of CHAPLE disease. Specific place in therapy for pozelimab not yet established.

Pozelimab-bbfg Dosage and Administration

General

Pretreatment Screening

Complete or update meningococcal vaccination (for serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) ≥2 weeks prior to administering the first dose of pozelimab, unless the risks of delaying therapy outweigh the risk of developing a meningococcal infection. Follow the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor.
If urgent therapy with pozelimab is indicated in a patient who is not up-to-date with vaccines for both MenACWY and MenB according to ACIP recommendations, administer meningococcal vaccine(s) as soon as possible and provide the patient with antibacterial drug prophylaxis prior to initiating pozelimab therapy.

Patient Monitoring

Monitor closely for signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected.
Monitor patients for 30 minutes for allergic reactions following the first IV infusion and first sub-Q injection.
Regularly test at risk (e.g., sexually active) patients for gonorrhea.

Other General Considerations

For the duration of pozelimab therapy, revaccinate in accordance with ACIP recommendations for meningococcal vaccines.
Vaccinate against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections in accordance with ACIP recommendations.

Administration

Administer loading dose by IV infusion (after dilution) and subsequent maintenance doses by sub-Q injection.

Available as single-dose vials containing 200 mg/mL.

Doses (IV and sub-Q) must be prepared and administered by a healthcare provider.

If a sub-Q maintenance dose is missed, administer as soon as possible within 3 days of the missed dose. If >3 days have passed since the missed dose, skip missed dose and resume usual dosing schedule; do not administer 2 doses on the same day to make up for a missed dose. In each case, patients can resume their regular once weekly dosing schedule. May adjust day of weekly administration if needed, as long as a minimum of 4 days (96 hours) elapses between doses.

IV Administration

Commercially available injection must be diluted prior to IV infusion.

Administer diluted solution immediately after preparation; if not used immediately, store as recommended by the manufacturer at room temperature or under refrigeration.

Infuse diluted solution through an IV line containing a sterile, in-line or add-on 0.2–5 micron filter. Do not coadminister other drugs through the same IV line. Observe patients for 30 minutes following completion of the infusion.

Dilution

Prior to dilution, remove vial(s) from fridge and allow to sit at room temperature (20–25°C) for ≥45 minutes.

Gently swirl vial(s) in an upright position; do not shake to avoid foaming. Withdraw calculated volume of pozelimab-bbfg from the vials using a 21-gauge stainless steel needle with Luer-Lok. Discard any unused drug remaining in the vials.

Dilute in an IV infusion bag containing 25–250 mL of either 0.9% sodium chloride injection or 5% dextrose injection to yield a final drug concentration of 6.7–20 mg/mL. Mix solution using gentle inversion; do not shake.

Rate of Administration

Infuse diluted solution over a minimum of 1 hour; do not exceed maximum rate of 1000 mg/hour.

Sub-Q Administration

Prior to use, remove vial(s) from fridge and allow to sit at room temperature (20–25°C) for ≥45 minutes.

Gently swirl vial(s) in an upright position; do not shake to avoid foaming. Withdraw calculated volume of pozelimab-bbfg from vials using a 21-gauge needle with Luer-Lok. Discard any unused drug remaining in the vials. Divide doses >400 mg into 2 separate injections. Change the syringe needle for administration to a 1/2 or 5/8-inch stainless steel 25-gauge to 27-gauge needle with Luer-Lok.

Inject dose into the abdomen, thigh, or upper arm, rotating sites. Avoid injecting into moles, scars, or areas where skin is tender, bruised, red, hard, or not intact. When administering multiple injections, administer injections consecutively, each at different sites.

Following administration of first sub-Q injection, observe patients for 30 minutes.

Administer sub-Q injections within 4 hours of preparation.

Dosage

Both IV infusion and sub-Q injections are required for complete dosing of pozelimab-bbfg.

Pediatric Patients

CD55-deficient PLE

IV, then Sub-Q

Pediatric patients ≥1 year of age: Loading dose of 30 mg/kg administered on Day 1 as IV infusion. Maintenance dose of 10 mg/kg sub-Q once weekly starting on Day 8; continue once weekly thereafter.

If inadequate clinical response after ≥3 weekly maintenance doses (i.e., from Week 4 onward), consider increasing dosage to 12 mg/kg once weekly. Maximum maintenance dosage: 800 mg once weekly. Separate doses >400 mg into 2 injections.

Adults

CD55-deficient PLE

IV, then Sub-Q

Loading dose of 30 mg/kg administered on Day 1 as IV infusion. Maintenance dose of 10 mg/kg sub-Q once weekly starting on Day 8; continue once weekly thereafter.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Pozelimab-bbfg

Contraindications

Unresolved Neisseria meningitidis infection.

Warnings/Precautions

Warnings

Serious Meningococcal Infections

Life-threatening and fatal meningococcal infections reported in vaccinated and unvaccinated patients receiving complement inhibitors (see Boxed Warning). Increased risk of meningococcal infections, including septicemia and/or meningitis. Serious and life-threatening infections can be caused by any serogroup, including nongroupable strains.

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

In patients not up-to-date with both MenACWY and MenB vaccines who require pozelimab-bbfg urgently, administer meningococcal vaccine(s) as soon as possible and antibacterial prophylaxis. Efficacy, duration, and regimens for antibacterial drug prophylaxis not evaluated in patients receiving complement inhibitors.

Because of complement inhibition, even with development of antibodies following vaccination, risk of meningococcal infection caused by nongroupable strains of N. meningitidis not eliminated.

Closely monitor for early signs and symptoms of meningococcal infection; immediately evaluate if infection suspected. Inform patients and caregivers of signs and symptoms; instruct them to seek immediate medical attention if signs and symptoms develop. If not recognized and treated early, meningococcal infection can become life-threatening or fatal. Withhold pozelimab-bbfg if a serious meningococcal occurs until infection has resolved.

Other Warnings and Precautions

Other Bacterial Infections

Potential for increased susceptibility to other encapsulated infections caused by N. meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and less frequently, Neisseria gonorrhoeae. May increase risk of serious infections from S. pneumoniae and H. influenzae type b (Hib).

Vaccinate patients against S. pneumoniae and Hib in accordance with ACIP guidelines. Increased risk of infection due to these organisms even with development of antibodies following vaccination. Withhold pozelimab-bbfg if a serious encapsulated bacterial infection occurs until infection has resolved. Counsel patients on gonorrhea prevention; advise patients to undergo regular gonorrhea testing if at risk (e.g. sexually active).

Systemic Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, reported.

Temporarily withhold pozelimab-bbfg and institute appropriate supportive care measures if signs of cardiovascular instability or respiratory compromise occur.

Immune Complex Formation

Formation of immune complexes reported during transition between complement inhibitors.

Consider potential for immune complex formation when switching between complement inhibitors.

Immunogenicity

In primary clinical trial, 9 of 10 patients ≥3 years of age with CD55-deficient PLE evaluable for antibodies against pozelimab. None of these patients developed anti-pozelimab-bbfg antibodies during the 48-week treatment period.

Data insufficient to characterize effect of anti-drug antibodies on pozelimab pharmacodynamics, pharmacokinetics, safety, and/or effectiveness.

Specific Populations

Pregnancy

No data available in pregnancy to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, monoclonal antibodies can be actively transported across the placenta.

Lactation

Not known if present in human or animal milk; endogenous maternal IgG and monoclonal antibodies known to transfer into human milk. Effects on breast-fed child or on milk production unknown; effects of local GI exposure and extent of systemic exposure to breast-fed child also unknown.

Weigh benefits of breast-feeding with mother's clinical need for pozelimab-bbfg and potential for adverse effects on breast-fed child from drug or from underlying maternal condition.

Pediatric Use

Safety and effectiveness established for treatment of CD55-deficient PLE in pediatric patients ≥1 year of age. Safety and effectiveness not established in pediatric patients <1 year of age.

Geriatric Use

Not studied in geriatric patients since CD55-deficient PLE is largely a pediatric disease.

Hepatic Impairment

Unlikely to undergo hepatic elimination.

Renal Impairment

Unlikely to undergo renal elimination.

Common Adverse Effects

Adverse effects reported in ≥2 patients include upper respiratory tract infection, fracture, urticaria, alopecia.

Drug Interactions

Formal drug interaction studies not conducted to date.

Specific Drugs

Drug

Interaction

Comments

IV immune globulin (IVIG)

Potential for decreased serum concentrations of pozelimab

Avoid concomitant use

If concomitant use cannot be avoided, monitor for worsening of CD55-deficient protein-losing enteropathy

Pozelimab-bbfg Pharmacokinetics

Absorption

Bioavailability

Estimated bioavailability following sub-Q injection of 600 mg in healthy patients: 51%.

Peak plasma concentrations attained at a median of 7 (range: 3–7) days following a single sub-Q injection of 300 mg or 600 mg.

Following once weekly sub-Q injection in patients with CD55-deficient protein-losing enteropathy, steady state concentrations attained after approximately 20 weeks.

Following single IV infusion in healthy patients, peak plasma concentrations exhibit dose-proportional increases; however, increases in mean AUC are greater than dose proportional (>16-fold) for total pozelimab serum concentrations between 3–30 mg/kg.

Special Populations

Not studied in geriatric patients.

Pharmacokinetics significantly affected by weight.

Distribution

Extent

Not known if distributed into human or animal milk.

Elimination

Metabolism

Expected to be metabolized in similar manner as endogenous IgG; degraded into small peptides and amino acids via catabolic pathways.

Elimination Route

Eliminated mainly via linear non-saturable proteolytic pathways at higher concentrations and predominantly via saturable C5 target-mediated pathways at lower concentrations.

Half-life

Single 30 mg/kg IV dose: 13.5 (range: 10–17.2) days.

Single 600 mg sub-Q dose: 14.1 (range: 8.6 to 17.3) days.

Stability

Storage

Parenteral

Injection, for IV or sub-Q use

Unopened vials: 2–8°C; store in original carton to protect from light. Do not freeze or shake.

Diluted IV solution: If not used immediately, may store at room temperature (25°C) for ≤8 hours from time of preparation to end of infusion; discard after 8 hours at room temperature. May also be stored under refrigeration at 2–8°C for ≤24 hours from time of preparation to end of infusion; discard unused solution after 24 hours if stored in refrigerator. If stored under refrigeration, allow to come to room temperature before administering. Do not freeze diluted IV solution.

Actions

Human monoclonal immunoglobulin G₄ ^P (IgG₄ ^P) antibody directed against terminal complement protein C5.
Inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby inhibiting formation of the membrane attack complex C5b-C9, which mediates cell lysis.
CD55-deficient PLE is a rare, life-threatening autosomal recessive disorder, also known as complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE) disease. The condition is caused by loss-of-function variants of the CD55 gene, which plays a crucial role in regulating the complement system.

Advice to Patients

Advise patients to read the FDA-approved patient labeling (Medication Guide).
Inform patients that they will be given a Patient Safety Card for pozelimab-bbfg that should be carried with them at all times and for 3 months after the last dose. Inform patients that this card describes symptoms of meningococcal infection or other infection, which, if experienced, should prompt them to seek immediate medical evaluation.
Advise patients of the risk of meningococcal infection. Inform patients of the signs and symptoms of meningococcal infection; if these occur, advise patients to seek immediate medical attention. Inform patients of the need to complete or update meningococcal vaccination for both MenACWY and MenB ≥2 weeks prior to receiving the first dose of pozelimab-bbfg and of the need to be revaccinated according to current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccines during pozelimab-bbfg therapy. Inform patients that vaccination may not prevent meningococcal infection.
Advise patients of the risk of other bacterial infections, especially those due to encapsulated bacteria. Inform patients of the need for vaccinations in accordance with current ACIP recommendations. Advise patients to report any new signs or symptoms of infection.
Counsel patients about gonorrhea prevention and advise patients at risk (e.g., sexually active patients) to seek regular testing.
Advise patients to notify their clinician and seek immediate medical attention if they experience any symptoms of systemic hypersensitivity reactions.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Pozelimab-bbfg is obtained through specialty designated pharmacies and distributors. Contact manufacturer for specific availability information.