AHFS Class:

• Hemostatics 20:28.16

Brands:

• Hympavzi^®

Generic Name(s):

• Marstacimab-hncq

Marstacimab-hncq is a tissue factor pathway inhibitor (TFPI) antagonist.1

Marstacimab-hncq has the following uses:

Marstacimab-hncq is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A (congenital factor VIII deficiency) without factor VIII inhibitors, or hemophilia B (congenital factor IX deficiency) without factor IX inhibitors. 1

General

Marstacimab-hncq is available in the following dosage form(s) and strength(s):

• Injection: 150 mg/mL in a single-dose prefilled syringe1
• Injection: 150 mg/mL in a single-dose prefilled pen1

Dosage

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

Adults

Dosage and Administration

• Administer by subcutaneous injection once weekly.1
• The recommended dosage of marstacimab-hncq is as follows: Loading dose: 300 mg (two 150 mg injections) by subcutaneous injection.1 Maintenance dose: One week after the loading dose, initiate maintenance dosing of 150 mg every week by subcutaneous injection on the same day each week, at any time of day.1
• Consider a dosage adjustment to 300 mg weekly in patients weighing greater than or equal to 50 kg when control of bleeding events is judged to be inadequate by the healthcare provider.1 Safety and efficacy of dosages above 300 mg weekly have not been established.1
• Factor VIII and factor IX products can be administered for the treatment of breakthrough bleeds in patients receiving marstacimab-hncq.1 Do not use additional doses of marstacimab-hncq to treat breakthrough bleeds.1
• Temporarily discontinue marstacimab-hncq before major surgery.1
• See Full Prescribing Information for additional dosing and administration instructions.1

Contraindications

None.1

Warnings/Precautions

Thromboembolic Events

Marstacimab-hncq is a tissue factor pathway inhibitor (TFPI) antagonist, and may increase the risk of thromboembolic complications.1

Marstacimab-hncq has not been studied in patients with a history of previous thromboembolic events.1 Interrupt marstacimab-hncq prophylaxis if diagnostic findings consistent with thromboembolism occur and manage as clinically indicated.1

If factor VIII or factor IX products are indicated in a patient receiving marstacimab-hncq prophylaxis, the minimum effective dose of factor VIII or factor IX according to the product label is recommended.1

Hypersensitivity

Marstacimab-hncq may cause hypersensitivity reactions (including, but not limited to urticaria and pruritus).1 If marstacimab-hncq-treated patients develop a severe hypersensitivity reaction, advise patients to discontinue the drug and seek immediate emergency treatment.1

Embryofetal Toxicity

Based on its mechanism of action, marstacimab-hncq may cause fetal harm when administered to a pregnant woman.1 Advise pregnant women of the potential risk to the fetus.1 Advise females of reproductive potential to use effective contraception during treatment with marstacimab-hncq and for 2 months after the last dose.1

Specific Populations

Pregnancy

Based on its mechanism of action, marstacimab-hncq may cause fetal harm when administered to a pregnant woman.1 There are no available data on marstacimab-hncq use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.1 Female animal reproduction studies have not been conducted with marstacimab-hncq.1 Although there are no data on marstacimab-hncq, monoclonal antibodies can be actively transported across the placenta, and marstacimab-hncq may cause fetal harm.1

The background risk of major birth defects and miscarriage for the indicated populations is unknown.1 All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.1 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.1

Lactation

There are no data on the presence of marstacimab-hncq in either human or animal milk, the effects on the breastfed child, or the effects on milk production. 1

Endogenous maternal IgG and monoclonal antibodies are known to be present in human milk.1 The effects of local GI exposure and limited systemic exposure in the breastfed child to marstacimab-hncq are unknown.1

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for marstacimab-hncq and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.1

Females and Males of Reproductive Potential

Marstacimab-hncq may cause fetal harm when administered to a pregnant woman.1

Verify the pregnancy status of females of reproductive potential prior to initiating marstacimab-hncq treatment.1

Advise female patients of reproductive potential to use effective contraception during treatment with marstacimab-hncq and for 2 months after the last dose.1

Pediatric Use

The safety and effectiveness of marstacimab-hncq to prevent or reduce the frequency of bleeding episodes in hemophilia A or B without inhibitors have been established in pediatric patients 12 years of age and older.1 Use of marstacimab-hncq for this indication is supported by evidence from an open-label, multicenter phase 3 study in 19 adolescents and 97 adults with hemophilia without inhibitors.1

The safety and effectiveness of marstacimab-hncq have not been established in pediatric patients younger than 12 years of age.1

Geriatric Use

One patient 65 years of age and older was enrolled in the clinical studies for hemophilia A or B without inhibitors.1 Clinical studies of marstacimab-hncq did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects.1

Common Adverse Effects

Adverse reactions reported in ≥3% of marstacimab-hncq-treated patients were injection site reaction, headache, and pruritus.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT): No clinically significant differences in standard measures of coagulation including aPTT and PT were observed following marstacimab-hncq therapy.1

Actions

Mechanism of Action

Marstacimab-hncq is a human monoclonal IgG1 antibody directed against the Kunitz domain 2 (K2) of tissue factor pathway inhibitor (TFPI) to neutralize TFPI activity and enhance coagulation.1 TFPI is the primary inhibitor of the extrinsic coagulation cascade and negatively regulates thrombin generation within the extrinsic pathway of coagulation by inactivating the protease functions of FXa/FVIIa/TF complex.1 TFPI binds to and inhibits the factor Xa active site via its second Kunitz inhibitor domain (K2).1

Advice to Patients

• Advise patients and/or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use).1
• Ensure that patients and caregivers who will administer marstacimab-hncq receive appropriate training and instruction on the proper storage, use and handling of marstacimab-hncq from a healthcare professional.1
• Inform patients and/or caregivers that marstacimab-hncq increases coagulation potential.1 Discuss the appropriate dosing of concomitant agents such as FVIII or FIX with the patient prior to starting on marstacimab-hncq prophylaxis.1 Advise the patient to seek immediate medical attention if any signs or symptoms of thromboembolism occur.1
• Inform patients and/or caregivers that hypersensitivity reactions such as rash and pruritus are possible.1 Advise patients to discontinue marstacimab-hncq and seek immediate emergency treatment if a severe hypersensitivity reaction occurs.1
• Advise female patients of reproductive potential to use effective contraception during treatment with marstacimab-hncq and for 2 months after the last dose.1 Advise patients to report known pregnancies. 1

Additional Information

AHFS first Release^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Pfizer Laboratories Div Pfizer Inc. HYMPAVZI^® (marstacimab-hncq) SUBCUTANEOUS prescribing information. 2024 Oct. [Web]