Overview
11 DESCRIPTION Pozelimab-bbfg, a complement inhibitor, is a recombinant monoclonal antibody (IgG4 isotype). Pozelimab-bbfg is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture and has an approximate molecular weight of 145 kDa. VEOPOZ (pozelimab-bbfg) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Pozelimab-bbfg is a human, monoclonal immunoglobulin G4 P (IgG4 P ) antibody directed against the terminal complement protein C5 that inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby blocking the formation of the membrane-attack complex (C5b-C9, a structure mediating cell lysis). 12.2 Pharmacodynamics The effect of pozelimab-bbfg on complement activity was measured by total complement hemolytic activity test (CH50). The magnitude and duration of reduction from baseline in CH50 by pozelimab-bbfg was dose dependent.
Indications
- 1 INDICATIONS AND USAGE VEOPOZ 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. VEOPOZ is a complement inhibitor 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. ( 1 )
Common Doses
- 30 mg
- 10 mg
- 12 mg
- 800 mg
Dosage
2 DOSAGE AND ADMINISTRATION See the full prescribing information for meningococcal vaccine and prophylaxis recommendations prior to the first dose of VEOPOZ. ( 2.1 ) Recommended Dosage: Day 1 (loading dose): Administer a single 30 mg/kg dose by intravenous infusion after dilution. ( 2.2 ) 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).
Black Box Warning
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update meningococcal vaccination (for serogroups A, C, W and Y, and serogroup B) at least 2 weeks prior to administering the first dose of VEOPOZ, unless the risks of delaying therapy outweigh the risk of developing a meningococcal infection.
Contraindications
- 4 CONTRAINDICATIONS VEOPOZ is contraindicated in: Patients with unresolved Neisseria meningitidis infection [see Warnings and Precautions (5.1) ] . VEOPOZ is contraindicated in patients with unresolved Neisseria meningitidis infection. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Meningococcal Infections [see Warnings and Precautions (5.1) ] Other Bacterial Infections [see Warnings and Precautions (5.2) ] Systemic Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Immune Complex Formation [see Warnings and Precautions (5.4) ] Most common adverse reactions (in two or more patients) are: upper respiratory tract infection, fracture, urticaria, and alopecia. ( 6.
Interactions
- 7 DRUG INTERACTIONS Intravenous Immunoglobulin : May decrease pozelimab concentrations; avoid concomitant use. If concomitant use cannot be avoided, monitor patients for worsening of clinical signs and symptoms of disease. ( 7.1 ) 7.1 Intravenous Immunoglobulin VEOPOZ has not been studied in combination with intravenous immunoglobulin. Intravenous immunoglobulin may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as pozelimab thereby decreasing serum pozelimab concentrations.