DRUG INTERACTIONS(summary)

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 decrease serum pozelimab concentrations.

Avoid concomitant use of intravenous immunoglobulin with VEOPOZ. If concomitant use cannot be avoided, monitor patients for worsening of clinical signs and symptoms of CD55-deficient PLE

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BRIEF SUMMARY-

POZELIMB-bbfg- (Aug 2023)

Indn-  To  treat 1 year and older with CD-SS patient   protein losing enrtropahy (PLE) also known a   as Chaple disease

Comp-   Injection: 400 mg/2 mL (200 mg/mL) in a single-dose via                  Recommended Dosage:                                                                                                     Day 1 (loading dose): Administer a single 30 mg/kg dose by intravenous 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 

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

CI-  contraindicated in patients with unresolved Neisseria meningitidis infection.

WARNINGS -

Other Bacterial Infections: Interrupt treatment  in patients who are undergoing treatment for a serious encapsulated bacterial infection until the infection is resolved.

Pat Inform-

Meningococcal Infection -                                                                                                Advise patients of the risk of meningococcal, and other bacterial infections.

 Inform patients of the need to complete or update meningococcal vaccination for both MenACWY and MenB at least 2 weeks prior to receiving the first dose  and to be revaccinated according to current ACIP recommendations for meningococcal vaccines while on  therapy.

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 35.

Name-                       VEOPOZ

Acive  Ingredient -  Pozelimab-bbfg

Pharmacological clssificiation-        To  treat 1 year and older with CD-SS patient                                                                 protein losing enrtropahy (PLE) also known a                                                               as Chaple disease

Date of Approval                               8/18/2023

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                     VEOPOZ™ safely and effectively.

See full prescribing information for VEOPOZ. VEOPOZ (pozelimab-bbfg) injection, for intravenous or subcutaneous use

Initial U.S. Approval: 2023

WARNING:                                                                                                            SERIOUS MENINGOCOCCAL INFECTIONS See full prescribing information for complete boxed warning

 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 at least 2 weeks prior to administering the first dose of VEOPOZ, unless the risks of delaying therapy outweigh the risks 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 VEOPOZ are at increased risk for invasive disease caused by N. meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

INDICATIONS AND USAGE -                                                                                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.

ADVERSE REACTIONS-

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

CONTRAINDICATIONS

 VEOPOZ is contraindicated in patients with unresolved Neisseria meningitidis infection.

WARNINGS AND PRECAUTIONS-

Other Bacterial Infections: Interrupt treatment with VEOPOZ in patients who are undergoing treatment for a serious encapsulated bacterial infection until the infection is resolved.

 Systemic Hypersensitivity Reactions: Interrupt infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory comprise occur.

 Immune Complex Formation: Transition between other complement inhibitors has resulted in decreased drug concentrations and possible hypersensitivity reactions. Consider this potential if switching complement inhibitors to VEOPOZ. 

DOSAGE AND ADMINISTRATION See the full prescribing information for meningococcal vaccine and prophylaxis recommendations prior to the first dose of VEOPOZ. 

Recommended Dosage:                                                                                                     Day 1 (loading dose): Administer a single 30 mg/kg dose by intravenous 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). o The maximum maintenance dosage is 800 mg once weekly.

 See full prescribing information for instructions on preparation and administration. 

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

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Inform patients that they will be given a Patient Safety Card for VEOPOZ that they should carry with them at all times. This card describes symptoms of meningococcal, or other infection, which, if experienced, should prompt the patient to seek immediate medical evaluation.

Meningococcal Infection -                                                                                                Advise patients of the risk of meningococcal, and other bacterial infections.

 Inform patients of the need to complete or update meningococcal vaccination for both MenACWY and MenB at least 2 weeks prior to receiving the first dose of VEOPOZ and to be revaccinated according to current ACIP recommendations for meningococcal vaccines while on VEOPOZ therapy.

 Inform patients that vaccination may not prevent meningococcal infection.

 Inform patients of the signs and symptoms of meningococcal infection and advise patients to seek immediate medical attention if any signs or symptoms of infection occur 

Other Bacterial Infections, Including Gonococcal Infection

 Inform patients of the increased risk of other bacterial infections, particularly those due to encapsulated bacteria.

 Inform patients of the need to receive vaccinations according to the ACIP recommendations.

 Advise patients to report any new signs and symptoms of infection.

 Counsel patients about gonorrhea prevention and advise patients at risk (e.g., sexually active) to seek regular testing [see Warnings and Precautions (5.2)].

Systemic Hypersensitivity Reactions Advise patients to notify the healthcare provider and seek immediate medical attention if they experience any symptoms of systemic hypersensitivity reactions 

Manufactured by: Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591-6707 U.S. License No. 1760 Marketed by: Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591

CLINICAL PHARMACOLOGY

Mechanism of action-

-Pozelimab-bbfg is a human, monoclonal immunoglobulin G4P (IgG4P) 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).

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.

3. Pharmacokinetics-                                                                                                       In healthy subjects, single intravenous infusions of VEOPOZ over approximately one hour resulted in dose proportional increases in mean Cmax, but greater than proportional increases in mean AUCinf (>16-fold) for total pozelimab concentrations in serum between 3 mg/kg and 30 mg/kg.

 Absorption-                                                                                                                      In healthy subjects, following subcutaneous injection of 600 mg, the bioavailability of pozelimab-bbfg is estimated as 51%.

The median (range) time to reach peak concentration was 7 (3 to 7) days following a single subcutaneous injection of 300 mg or 600 mg in healthy subjects.

Distribution -                                                                                                                     In healthy adult subjects with a mean body weight of 70 kg, the mean (SD) volume of distribution following a single intravenous dose of 30 mg/kg was 3.3 (0.4) L.

The mean (SD) apparent volume of distribution following a single subcutaneous injection of 300 mg and 600 mg was 6.0 (0.9) L and 8.6 (2.7) L, respectively.

Elimination -                                                                                                                Pozelimab-bbfg is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Pozelimab-bbfg elimination is mediated via linear and non-linear pathways.

Specific Populations -                                                                                                  Body Weight Body weight was a significant covariate on the pharmacokinetics of pozelimab-bbfg. Renal and Hepatic Impairment Pozelimab-bbfg, a monoclonal antibody, is not likely to undergo renal or hepatic excretion.

Drug Interaction Studies-                                                                                                   Drug interaction studies have not been conducted.

Intravenous Immunoglobulin (IVIg) may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as pozelimab-bbfg, which may decrease serum pozelimab concentrations 

1 USE IN SPECIFIC POPULATIONS-

Pregnancy Risk Summary-                                                                                           Although there are no data on VEOPOZ 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; see Data).

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.

2. Lactation Risk Summary-                                                                                     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.

The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for VEOPOZ and any potential adverse effects on the breastfed infant from VEOPOZ or from the underlying maternal condition.

3. Pediatric Use-                                                                                                            The safety and effectiveness of VEOPOZ for the treatment of CD55-deficient PLE have been established in pediatric patients 1 year of age and older. Use of VEOPOZ for this indication is supported by a single-arm study in 10 patients with active CD55-deficient PLE 

The safety and effectiveness of VEOPOZ have not been established in pediatric patients less than 1 year of age. 8.5 Geriatric Use CD55-deficient PLE is largely a disease of pediatric patients. VEOPOZ has not been studied in the geriatric population.