Marstacimab-hncq (Monograph)

Brand name: Hympavzi
Drug class: Hemostatics

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Recombinant human monoclonal antibody (IgG type 1) that binds to tissue factor pathway inhibitor (TFPI).

Uses for Marstacimab-hncq

Hemophilia A and B

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients ≥12 years of age with hemophilia A (congenital factor VIII deficiency) without factor VIII inhibitors, or hemophilia B (congenital factor IX deficiency) without factor IX inhibitors.

Designated an orphan drug by FDA for treatment of patients with hemophilia A and hemophilia B with or without inhibitors.

The World Federation of Hemophilia (WFH) and the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation publish guidelines on the management of hemophilia.

Prophylactic therapy with clotting factor concentrates or other non-factor replacement product is considered the current standard of care for patients with severe hemophilia A or severe hemophilia B. Prophylaxis also may be considered in patients with mild or moderate hemophilia A or B depending on their risk of bleeding.

Individualize specific treatment strategy based on patient's age at the time of prophylaxis initiation, bleeding phenotype, joint status, individual pharmacokinetics, lifestyle, and preference for choice of therapy.

Marstacimab-hncq Dosage and Administration

General

Pretreatment Screening

Prior to treatment, obtain negative pregnancy test in female patients with reproductive potential.

Patient Monitoring

Monitor for signs and symptoms of thromboembolism.

Other General Considerations

When switching from prophylactic factor concentrate replacement therapy to marstacimab, discontinue the factor VIII or IX concentrate. Marstacimab-hncq may be initiated immediately after discontinuation. Data are not available for patients transitioning from non-factor-based hemophilia treatments to marstacimab-hncq.
Do not use additional marstacimab-hncq doses to treat breakthrough bleeds; factor VIII or IX concentrates may be used.
Discontinue marstacimab-hncq prior to major surgery and manage with clotting factor concentrates and thrombosis risk mitigation strategies. Resume marstacimab-hncq based on the patient's clinical status, including thromboembolic risks.
Limited experience exists with marstacimab-hncq in acute severe illness. Consider temporarily withholding the drug in cases of increased coagulation risk (e.g., serious infection, sepsis, trauma). Manage acute illness per local standards and evaluate the risks before continuing marstacimab-hncq. Resume therapy once the patient has clinically recovered.

Administration

Sub-Q Administration

Administer by sub-Q injection only.

Available as a 150 mg/mL single-dose prefilled syringe or a 150 mg/mL single-dose prefilled pen with needle guard.

Prior to administration, remove prefilled syringe or pen from refrigerator and warm to room temperature (15–30 minutes) in original carton, away from direct sunlight; do not use a heat source. Use within 7 days after removal or discard.

Use under guidance of a healthcare provider.

Train patients and caregivers in preparation and administration before self-injection.

Administer sub-Q injections into abdomen or thigh (preferred injection sites). Injections in the upper arm (prefilled syringe only) or buttocks (prefilled pen only) should only be performed by a caregiver or healthcare provider.

Avoid injecting into bruised, tender, scarred, or bony areas, and rotate injection sites with each dose.

Inject other sub-Q medications preferably into separate anatomical sites.

Dosage

Pediatric Patients

Hemophilia A or B without Inhibitors

Sub-Q

Pediatric patients ≥12 years of age: Initially, 300 mg (two 150-mg injections), followed by maintenance dosage of 150 mg every week. A maintenance dosage of 300 mg weekly may be needed in patients weighing ≥50 kg.

Administer the maintenance dose on the same day each week, at any time of day.

Missed dose in patients receiving 150 mg maintenance dose: Administer missed dose as soon as possible before the day of the next scheduled dose, then resume the usual weekly 150-mg dose schedule (at the same schedule as prior to the missed dose or new schedule based on the date of administration of the missed dose). If >13 days have passed since the last dose was administered, administer a 300 mg loading dose, then resume the 150 mg weekly schedule.

Missed dose in patients receiving 300 mg maintenance dose: Administer missed dose as soon as possible and then resume the usual weekly 300-mg dose schedule (at the same schedule as prior to the missed dose or new schedule based on the date of administration of the missed dose).

Adults

Hemophilia A or B without Inhibitors

Sub-Q

Initially, 300 mg (two 150-mg injections), followed by maintenance dosage of 150 mg every week. A maintenance dosage of 300 mg weekly may be needed in patients weighing ≥50 kg

Administer the maintenance dose on the same day each week, at any time of day.

Missed dose in patients receiving 150 mg maintenance dose: Administer missed dose as soon as possible before the day of the next scheduled dose, then resume usual weekly 150-mg dose schedule (at the same schedule as prior to the missed dose or new schedule based on the date of administration of the missed dose). If >13 days have passed since the last dose was administered, administer a 300 mg loading dose, then resume the 150 mg weekly schedule.

Missed dose in patients receiving 300 mg maintenance dose: Administer missed dose as soon as possible and then resume usual weekly 300-mg dose schedule (at the same schedule as prior to the missed dose or new schedule based on the date of administration of the missed dose).

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Marstacimab-hncq

Contraindications

None.

Warnings/Precautions

Thromboembolic Events

May increase the risk of thromboembolic complications; not studied in patients with a history of thromboembolic events. Interrupt therapy if thromboembolism suspected and manage as clinically appropriate. Use minimal effective factor VIII or IX concentrate dosage if required during marstacimab-hncq therapy.

Hypersensitivity

Hypersensitivity reactions reported. Discontinue marstacimab-hncq and administer appropriate therapy if clinically significant hypersensitivity reaction occurs.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; advise female patients of reproductive potential to use effective contraception during treatment and for 2 months after the last dose.

Immunogenicity

Anti-drug antibodies (ADAs), including neutralizing antibodies, detected. ADAs reduced drug concentrations but showed no clinical impact on safety or efficacy over 12 months.

Specific Populations

Pregnancy

May cause fetal harm based on mechanism of action. Insufficient data to assess the risks of birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation

No data on presence of marstacimab-hncq in human or animal milk, or whether the drug has any effects on the breastfed child or on milk production.

Females and Males of Reproductive Potential

May cause fetal harm. Confirm pregnancy status before starting therapy. Advise female patients of reproductive potential to use effective contraception during treatment and for 2 months after the last dose.

Pediatric Use

Safety and efficacy established in patients ≥12 years of age. Safety and efficacy in patients ≤12 years of age not established.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine if they respond differently than younger patients.

Hepatic Impairment

Marstacimab-hncq pharmacokinetics show no significant changes in mild hepatic impairment; effects in moderate to severe impairment are unknown.

Renal Impairment

Marstacimab-hncq pharmacokinetics show no changes in mild renal impairment; effects in moderate to severe impairment are unknown.

Common Adverse Effects

Most common adverse reactions (≥3%): injection site reaction, headache, pruritus.

Drug Interactions

Does not cause clinically significant changes in activated partial thromboplastin time (aPTT) or prothrombin time (PT).

Effects on the pharmacokinetics of other drugs have not been established.

Marstacimab-hncq Pharmacokinetics

Absorption

Bioavailability

Approximately 71%

Plasma Concentrations

Steady-state concentrations achieved by approximately 60 days (dose 8 or 9).

Distribution

Special Populations

Higher exposure in lower-weight patients.

Elimination

Half-life

7 to 10 days.

Metabolism

Exhibits dose-dependent pharmacokinetics and undergoes target-mediated drug disposition (TMDD), accelerating clearance at lower doses due to TFPI binding but slowing at higher doses as binding sites saturate, shifting elimination to non-target pathways.

Similar to IgG, metabolized by catabolic pathways into small peptides and amino acids.

Special Populations

Clearance 29% lower in adolescents 12–18 years of age compared to adults.

Stability

Storage

Parenteral

Prefilled Pen and Syringe

Store in refrigerator at 2–8°C in original carton to protect from light.

May store at room temperature (≤30°C) for up to 7 days. Do not refrigerate after removal; discard after 7 days.

Do not freeze or shake.

Actions

Recombinant human monoclonal antibody (IgG type 1) that binds to tissue factor pathway inhibitor (TFPI).
TFPI inhibits thrombin generation in the extrinsic coagulation pathway by interacting with factor Xa and the factor Xa/factor VIIa/tissue factor complex.
Marstacimab-hncq neutralizes TFPI, reducing factor Xa inhibition and increasing thrombin formation to enhance hemostasis.

Advice to Patients

Advise patients and/or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
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.
Inform patients and/or caregivers that marstacimab-hncq increases coagulation potential. Discuss the appropriate dosing of concomitant agents such as factor VIII or factor IX concentrates with the patient prior to starting on marstacimab-hncq prophylaxis. Advise the patient to seek immediate medical attention if any signs or symptoms of thromboembolism occur.
Inform patients and/or caregivers that hypersensitivity reactions such as rash and pruritus are possible. Advise patients to discontinue marstacimab-hncq and seek immediate emergency treatment if a severe hypersensitivity reaction occurs.
Advise female patients of reproductive potential to use effective contraception during treatment with marstacimab-hncq and for 2 months after the last dose. Advise patients to report known or suspected pregnancies or if they are breastfeeding or plan to breastfeed.
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.
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.

Marstacimab-hncq is available through designated specialty pharmacies. Contact manufacturer or consult the marstacimab-hncq website ([Web]) for specific information.