Hympavzi (Marstacimab)
Anti-TFPI Monoclonal Antibody for Bleeding Prevention in Severe Hemophilia
Quick Facts About Hympavzi
Key Takeaways About Hympavzi
- Novel mechanism of action: Hympavzi works by blocking TFPI, a natural anticoagulant, rather than replacing the missing clotting factor – offering a fundamentally different approach to hemophilia prophylaxis
- Convenient once-weekly injection: Administered subcutaneously via a pre-filled pen, eliminating the need for frequent intravenous factor infusions
- For severe hemophilia without inhibitors: Approved for patients aged 12+ with severe hemophilia A or B (factor levels below 1%) who have not developed factor inhibitors
- Blood clot risk: Hympavzi can cause thromboembolic events; patients must be aware of the signs and symptoms of blood clots and seek immediate medical attention
- Factor replacement still needed: Patients may require factor VIII or IX products for breakthrough bleeds while on Hympavzi, under careful medical guidance
What Is Hympavzi and What Is It Used For?
Hympavzi (marstacimab) is a monoclonal antibody used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients aged 12 years and older with severe hemophilia A (factor VIII deficiency) or severe hemophilia B (factor IX deficiency) who have not developed inhibitors against their replacement clotting factors.
Hympavzi contains the active substance marstacimab, a fully human monoclonal antibody specifically designed to recognize and bind to a protein in the body called tissue factor pathway inhibitor (TFPI). TFPI is a naturally occurring anticoagulant protein that normally prevents excessive blood clotting. In healthy individuals, TFPI serves an important regulatory function by keeping the coagulation process in balance. However, in patients with hemophilia who already have impaired clotting ability, the action of TFPI further limits their capacity to form blood clots when needed.
By binding to and neutralizing TFPI, marstacimab effectively removes one of the body's natural brakes on clotting. This allows increased generation of thrombin – a key enzyme in the coagulation cascade that converts fibrinogen to fibrin, forming the structural foundation of blood clots. The result is an improved hemostatic balance that helps patients with hemophilia form clots more effectively when injury occurs, thereby reducing spontaneous and trauma-related bleeding episodes.
Hemophilia A is an inherited bleeding disorder caused by a deficiency of clotting factor VIII, affecting approximately 1 in 5,000 male births worldwide. Hemophilia B, also known as Christmas disease, is caused by a deficiency of clotting factor IX and affects approximately 1 in 25,000 male births. Both conditions are X-linked recessive disorders, meaning they predominantly affect males, while females are typically carriers. In severe forms of both conditions (factor levels below 1% of normal), patients experience frequent spontaneous bleeding into joints, muscles, and other tissues, which without adequate prophylaxis can lead to chronic joint damage, disability, and potentially life-threatening hemorrhages.
Hympavzi represents a significant advancement in hemophilia treatment as a non-factor replacement therapy. Traditional hemophilia management has relied on regular intravenous infusions of the missing clotting factor (factor VIII for hemophilia A, factor IX for hemophilia B). While effective, these factor replacement therapies often require multiple weekly intravenous infusions, which can be burdensome for patients. Hympavzi offers an alternative approach by targeting the coagulation pathway through a different mechanism, administered as a simple subcutaneous injection once per week.
Hympavzi is specifically indicated for patients with severe hemophilia who have not developed inhibitors (antibodies against replacement factor VIII or IX). Some patients with hemophilia develop these inhibitors, which render standard factor replacement therapy less effective. Hympavzi has not been studied in patients with inhibitors, and its use in this population is not approved. Patients who develop inhibitors should discuss alternative treatment options with their hematologist.
What Should You Know Before Using Hympavzi?
Before starting Hympavzi, inform your doctor about all your medical conditions, particularly any history of blood clots, cardiovascular disease, or thrombophilia. Do not use Hympavzi if you are allergic to marstacimab or any of the excipients.
Contraindications
You should not use Hympavzi if:
- Allergy to marstacimab or any excipient – if you are allergic to marstacimab or any of the other ingredients in Hympavzi (disodium edetate, L-histidine, L-histidine monohydrochloride, polysorbate 80, sucrose, or water for injections), do not use this medicine. If you are unsure whether you have an allergy, consult your doctor, pharmacist, or nurse before using Hympavzi
Warnings and Precautions
Talk to your doctor before using Hympavzi. It is essential to discuss any of the following risk factors or conditions with your healthcare provider, as they may affect the safety of treatment:
Hympavzi promotes blood clotting and can cause blood clots in blood vessels, which may be life-threatening. Tell your doctor if you have any of the following conditions that increase your risk:
- Previous history of coronary artery disease or ischemic heart disease
- Previous history of blood clots in veins or arteries (deep vein thrombosis, pulmonary embolism)
- Genetic thrombophilia (e.g., Factor V Leiden mutation, Protein C or S deficiency)
- Prolonged immobility or bed rest
- Obesity
- Smoking
- Serious infections or sepsis
- Major trauma or crush injuries
- Cancer
Stop using Hympavzi and seek immediate medical attention if you experience any signs or symptoms of a blood clot, including:
- Swelling, pain, redness, or discoloration in arms or legs
- Shortness of breath or difficulty breathing
- Chest pain or pain in the upper back
- Rapid heartbeat or coughing up blood
- Feeling faint, severe headache, or facial numbness
- Eye pain, swelling, or vision problems
Use with Other Hemophilia Treatments
Before starting Hympavzi, it is critically important to discuss with your doctor how to manage the transition from your current hemophilia treatment. Your healthcare team will provide specific instructions on how to discontinue your current factor or non-factor therapy when switching to Hympavzi.
You may still need to use factor VIII or factor IX replacement products to treat breakthrough bleeding episodes while on Hympavzi. However, the combined use of Hympavzi with factor products may increase the risk of thromboembolic events. You must follow your healthcare provider's instructions carefully regarding when and how to use factor replacement alongside Hympavzi.
Allergic Reactions
Symptoms of allergic reactions have been observed in patients using Hympavzi. Stop using Hympavzi and seek immediate medical attention if you experience signs of a potentially serious allergic reaction, including:
- Rash, hives (urticaria), or itching
- Swelling of the face, lips, tongue, or throat
- Difficulty breathing or swallowing
- Dizziness or lightheadedness
Pregnancy and Breastfeeding
If you are able to become pregnant, you should use effective contraception during treatment with Hympavzi and for at least 1 month after the last injection.
If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. Your doctor will carefully weigh the benefits of using Hympavzi against the potential risks to your unborn child. There is limited data available on the use of marstacimab in pregnant women, and the potential effects on fetal development are not fully known.
If you are breastfeeding, consult your doctor about whether you should stop breastfeeding or stop using Hympavzi. Your doctor will consider the benefit of treatment for you against the benefit of breastfeeding for your baby. It is not known whether marstacimab passes into human breast milk.
Children and Adolescents
Hympavzi should not be used in children under 1 year of age and is not recommended for children under 12 years of age. The safety and efficacy of this medicine have not been established in this age group. Adolescents aged 12 years and older weighing at least 35 kg may use Hympavzi, and they can self-inject provided that their doctor or nurse and parent or caregiver agree and the patient has been properly trained.
Driving and Operating Machinery
Hympavzi has no or negligible effect on the ability to drive and use machines. No dose adjustment or precautions are necessary for patients who drive or operate machinery while using Hympavzi.
Important Information About Excipients
Hympavzi contains polysorbate 80 (0.2 mg per mL), which can cause allergic reactions in some people. Tell your doctor if you have any known allergies to polysorbate. This medicine also contains less than 1 mmol (23 mg) sodium per 1 mL dose, meaning it is essentially sodium-free.
How Does Hympavzi Interact with Other Drugs?
Hympavzi can interact with other hemophilia treatments and medications that affect blood clotting. Tell your doctor about all medications you are taking, including prescription drugs, over-the-counter products, and supplements.
Because Hympavzi works by enhancing blood clotting through inhibition of TFPI, its most clinically significant interactions are with other medications that also affect the coagulation cascade. The combination of Hympavzi with other procoagulant or anticoagulant therapies requires careful medical supervision to avoid either excessive clotting or inadequate bleeding protection.
Interactions with Hemophilia Treatments
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Factor VIII concentrates | Clotting factor replacement | Combined procoagulant effect may increase risk of thromboembolism | Use only for breakthrough bleeds; follow physician dosing instructions carefully |
| Factor IX concentrates | Clotting factor replacement | Combined procoagulant effect may increase risk of thromboembolism | Use only for breakthrough bleeds; follow physician dosing instructions carefully |
| Emicizumab (Hemlibra) | Bispecific antibody (non-factor therapy) | Multiple procoagulant mechanisms combined may significantly increase thrombotic risk | Switching protocol must be managed by a hemophilia specialist; adequate washout period required |
| Activated prothrombin complex concentrates (aPCC) | Bypassing agent | High risk of thrombotic microangiopathy and thromboembolism when combined | Avoid concurrent use if possible; use under strict specialist supervision only |
Other Drug Interactions
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Anticoagulants (warfarin, heparin, DOACs) | Blood thinners | Opposing mechanisms – anticoagulants reduce clotting while Hympavzi promotes it | Inform your doctor; dose adjustments and monitoring may be required |
| Antiplatelet agents (aspirin, clopidogrel) | Platelet inhibitors | May partially counteract the procoagulant effect of Hympavzi | Discuss the balance of thrombotic and bleeding risk with your doctor |
| Tranexamic acid | Antifibrinolytic | Additive procoagulant effect may increase risk of clotting | Use with caution under medical supervision; monitor for signs of thrombosis |
| Hormonal contraceptives | Estrogen-containing products | Estrogen increases baseline thrombotic risk | Discuss contraceptive options with your doctor; non-estrogen methods may be preferred |
Always inform your doctor, pharmacist, or nurse about all medicines you are currently taking, have recently taken, or might take. This includes over-the-counter medicines, vitamins, and herbal supplements. Your healthcare team will determine the safest combination of treatments for your individual situation.
What Is the Correct Dosage of Hympavzi?
Hympavzi is given as a subcutaneous injection. Treatment starts with a loading dose of 300 mg (two 150 mg injections), followed by a maintenance dose of 150 mg once weekly. Your doctor may increase the maintenance dose up to 300 mg weekly based on your response.
Treatment with Hympavzi should be initiated under the supervision of a physician experienced in the management of hemophilia. Always use this medicine exactly as your doctor has instructed. Check with your doctor or pharmacist if you are unsure about any aspect of your treatment.
Dosing Schedule
Loading Dose (Week 1)
300 mg administered as two separate 150 mg subcutaneous injections at different injection sites. This higher initial dose rapidly builds up the drug concentration in your body.
Maintenance Dose (Week 2 Onwards)
150 mg subcutaneous injection once weekly, on the same day each week. Depending on your response, your doctor may increase the maintenance dose up to a maximum of 300 mg weekly.
| Patient Group | Loading Dose | Maintenance Dose | Frequency |
|---|---|---|---|
| Adults (18+ years, ≥35 kg) | 300 mg (2 × 150 mg) | 150 mg (up to 300 mg) | Once weekly |
| Adolescents (12–17 years, ≥35 kg) | 300 mg (2 × 150 mg) | 150 mg (up to 300 mg) | Once weekly |
| Children (<12 years) | Not recommended | Not recommended | N/A |
How to Administer Hympavzi
Hympavzi is given as an injection under the skin (subcutaneous injection). It must not be injected into a blood vessel or muscle. Before your first self-injection, your doctor or nurse will demonstrate the correct technique.
Recommended injection sites:
- Abdomen (stomach area) – at least 5 cm away from the navel
- Thigh – front of the upper thigh
- Buttocks – only when administered by a caregiver, doctor, or nurse
Rotate the injection site with each dose. You may use the same body area but select a different spot within that area. Do not inject into skin that is red, tender, hard, or bruised, or into areas with scars or stretch marks. If more than one injection is needed for a full dose, each injection should be given at a different site.
For improved comfort, remove Hympavzi from the refrigerator and allow it to warm to room temperature in the carton (away from direct sunlight) for approximately 15 to 30 minutes before injection. Do not warm it using any other method (such as microwave or hot water).
Missed Dose
If you forget your scheduled dose, inject the missed dose as soon as possible before the day of your next scheduled dose. Then continue injecting the medicine as planned. Do not inject a double dose to make up for a forgotten dose.
If you have missed two consecutive scheduled doses (more than 13 days since your last injection), contact your doctor as soon as possible for guidance on how to restart treatment.
Overdose
If you have used more Hympavzi than prescribed, tell your doctor immediately. An overdose may increase the risk of thromboembolic events (blood clots), and you may need medical monitoring. Always use this medicine exactly as directed and consult your healthcare team if you have any questions about your dosing.
Stopping Treatment
Do not stop using Hympavzi without consulting your doctor. If you discontinue treatment, you may no longer be protected against bleeding episodes. Your doctor will advise you on how to safely transition to an alternative hemophilia treatment if needed.
Record the product name and batch number each time you use Hympavzi. Note the day of the week you inject to help you remember your weekly schedule. This information is important for tracking your treatment and for safety reporting purposes.
What Are the Side Effects of Hympavzi?
Like all medicines, Hympavzi can cause side effects, although not everybody gets them. The most common side effect is injection site reactions, occurring in more than 1 in 10 patients. Serious but uncommon side effects include blood clots and severe allergic reactions.
Understanding the possible side effects of Hympavzi is important so that you can recognize them early and seek appropriate medical advice. Side effects are classified by how frequently they occur based on data from clinical trials. Most side effects are mild to moderate and tend to diminish over time as your body adjusts to the treatment.
Serious Side Effects
Hympavzi can cause serious side effects that require immediate medical attention:
Skin rash (observed in up to 1 in 100 people) may sometimes be severe. Contact your doctor immediately if you develop a severe skin rash. Do not use Hympavzi again until you have spoken with your doctor about your rash.
Blood clots (thromboembolism) (observed in up to 1 in 100 people). Stop using Hympavzi and contact your doctor immediately if you notice signs or symptoms of a blood clot. See the Warnings and Precautions section for a complete list of symptoms to watch for.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Injection site reactions (itching, swelling, redness, pain, bruising, or hardening at the injection site)
Common
May affect up to 1 in 10 people
- Headache
- High blood pressure (hypertension)
- Itching (pruritus)
Uncommon
May affect up to 1 in 100 people
- Skin rash (may be severe)
- Blood clots (thromboembolic events)
- Allergic reactions
Managing Injection Site Reactions
Injection site reactions are the most frequently reported side effect. These reactions typically include localized itching, swelling, redness, pain, bruising, or induration (hardening) at the injection site. They are usually mild and resolve on their own within a few days. To minimize injection site reactions:
- Rotate injection sites with each dose
- Allow the medicine to warm to room temperature before injecting
- Apply a cold compress to the injection site if swelling or redness occurs
- Contact your doctor if reactions become severe or do not improve
Stop using Hympavzi and contact emergency services or go to the nearest emergency department if you experience signs of a severe allergic reaction (difficulty breathing, swelling of the face or throat) or signs of a blood clot (chest pain, sudden shortness of breath, leg swelling or pain, sudden severe headache, or vision changes).
How Should You Store Hympavzi?
Store Hympavzi in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Keep in the original carton to protect from light. If needed, it can be stored at room temperature (up to 30°C / 86°F) for up to 7 days.
Proper storage of Hympavzi is essential to maintain the effectiveness and safety of the medicine. As a biological product (monoclonal antibody), Hympavzi is sensitive to temperature, light, and physical stress. Follow these storage guidelines carefully:
- Refrigerator storage: Keep Hympavzi between 2°C and 8°C (36°F and 46°F). Store the pre-filled pen in the original carton to protect it from light
- Do not freeze: Freezing can damage the protein structure of the monoclonal antibody and render the medicine ineffective. If Hympavzi has been frozen, do not use it
- Room temperature storage: If necessary, Hympavzi can be removed from the refrigerator and stored at room temperature (up to 30°C / 86°F) in the original carton for up to 7 days. Once removed from the refrigerator, do not return it to the refrigerator. Discard any pen that has been at room temperature for more than 7 days, even if it still contains unused medicine
- Do not shake: Shaking can damage the monoclonal antibody protein and may cause the solution to become cloudy or form particles
- Inspect before use: Before injecting, check that the solution is clear and colorless to slightly yellow. Do not use if the solution is cloudy, dark yellow, or contains flakes or particles
- Check the expiry date: Do not use Hympavzi after the expiry date (EXP) printed on the pre-filled pen label and carton. The expiry date refers to the last day of that month
- Keep out of reach of children: Store this medicine out of the sight and reach of children
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.
What Does Hympavzi Contain?
Each Hympavzi pre-filled pen contains 150 mg of marstacimab as the active substance, along with inactive ingredients including disodium edetate, L-histidine, polysorbate 80, sucrose, and water for injections.
Active Ingredient
The active substance is marstacimab, a fully human immunoglobulin G1 (IgG1) monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. Each pre-filled pen delivers 150 mg of marstacimab in solution for subcutaneous injection.
Inactive Ingredients (Excipients)
- Disodium edetate – a chelating agent that helps stabilize the formulation
- L-histidine – an amino acid used as a buffer to maintain the pH of the solution
- L-histidine monohydrochloride – works in conjunction with L-histidine as a buffer system
- Polysorbate 80 (E 433) – a surfactant that prevents protein aggregation (may cause allergic reactions in sensitive individuals)
- Sucrose – a stabilizer that protects the protein during storage
- Water for injections – the solvent for the formulation
Appearance and Packaging
Hympavzi is a clear, colorless to slightly yellow solution for injection provided in a single-use pre-filled pen. Each carton contains 1 pre-filled pen. The pen is designed for single use only and should not be reused. After injection, the needle guard automatically covers the needle for safe disposal.
The marketing authorization holder is Pfizer Europe MA EEIG (Brussels, Belgium), and the manufacturer is Pfizer Manufacturing Belgium NV (Puurs-Sint-Amands, Belgium). For further information about this medicine, contact the local representative of the marketing authorization holder in your country.
Frequently Asked Questions About Hympavzi
References
- European Medicines Agency (EMA). Hympavzi (marstacimab) – Summary of Product Characteristics. European Public Assessment Report. 2024.
- Pfizer Inc. Hympavzi (marstacimab-hncq) Prescribing Information. U.S. Food and Drug Administration. 2024.
- Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1–158.
- Pasi KJ, Rangarajan S, Engelen ET, et al. Marstacimab for the prevention of bleeding episodes in patients with severe hemophilia: phase 2 clinical trial results. Blood. 2023;142(Suppl 1):Abstract.
- Mancuso ME, Mahlangu JN, Engelen ET, et al. Marstacimab, an anti-TFPI monoclonal antibody, for prophylaxis in patients with severe hemophilia: BASIS trial results. New England Journal of Medicine. 2024.
- World Federation of Hemophilia (WFH). Report on the Annual Global Survey 2023. Montreal: WFH; 2024.
- International Society on Thrombosis and Haemostasis (ISTH). ISTH SSC communication on non-factor therapies in hemophilia. Journal of Thrombosis and Haemostasis. 2023.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- Pipe SW, Shima M, Engelen ET, et al. Anti-TFPI therapy in hemophilia: mechanism of action and clinical implications. Blood Advances. 2023;7(15):4126–4137.
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