HYMPAVZI

Marstacimab‑hncq is a tissue factor pathway inhibitor (TFPI) antagonist, human monoclonal immunoglobulin G Type 1 (IgG1) antibody. Marstacimab‑hncq is produced by Chinese hamster ovary (CHO) cells by recombinant DNA technology and has a molecular mass of approximately 146 kDa. HYMPAVZI (marstacimab‑hncq) injection is supplied as a sterile, preservative-free solution for subcutaneous administration. The drug product is supplied as either a single-dose 150 mg/mL prefilled syringe or as a single‑dose 150 mg/mL prefilled pen. The solution of marstacimab‑hncq is clear and colorless to light yellow with a pH of 5.8. Each 150 mg/mL prefilled syringe or prefilled pen delivers 1 mL of HYMPAVZI. Each 1 mL of HYMPAVZI contains 150 mg of marstacimab‑hncq, and the inactive ingredients edetate disodium (0.05 mg), histidine (1.12 mg), L-histidine monohydrochloride (2.67 mg), polysorbate 80 (0.2 mg), and sucrose (85 mg), in Water for Injection, USP.

HYMPAVZI 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. HYMPAVZI is a tissue factor pathway inhibitor (TFPI) antagonist 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 )

• See Full Prescribing Information for important dosing and administration instructions. ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 , 2.6 ) • The recommended dosage of HYMPAVZI is: o Loading dose: 300 mg (two 150 mg injections) by subcutaneous injection o 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. ( 2.1 ) • Dose adjustment to 300 mg subcutaneous injection weekly can be considered. ( 2.1 ) • Factor VIII and factor IX products can be administered for the treatment of breakthrough bleeds in patients receiving HYMPAVZI. Do not use additional doses of HYMPAVZI to treat breakthrough bleeds. ( 2.4 ) • Temporarily discontinue HYMPAVZI before major surgery. ( 2.5 ) 2.1 Recommended Dosage For subcutaneous use only. The recommended dosage of HYMPAVZI for adult and pediatric patients 12 years of age and older is as follows: Loading Dose 300 mg (two 150 mg subcutaneous injections) If more than one injection is required to deliver a complete dose, administer each injection at a different injection site. 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. Dose Adjustment During Treatment Consider a dose adjustment to 300 mg subcutaneous injection 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. Safety and efficacy of HYMPAVZI at doses above 300 mg weekly have not been established. If more than one injection is required to deliver a complete dose, administer each injection at a different injection site. Missed Doses For patients on a maintenance dose of 150 mg: If a dose is missed, administer as soon as possible before the day of the next scheduled dose, and then resume usual 150 mg subcutaneous weekly dosing schedule (same schedule as prior to the missed dose or new schedule based on date of administration of missed dose). If more than 13 days have passed since the last dose was administered, administer a loading dose of 300 mg by subcutaneous injection followed by a resumption of 150 mg by subcutaneous injection once weekly thereafter. For patients on a maintenance dose of 300 mg: If one or more doses are missed, administer a dose as soon as possible, and then resume 300 mg subcutaneous weekly dosing schedule (same schedule as prior to the missed dose or new schedule based on date of administration of missed dose). 2.2 Preparation and Administration • HYMPAVZI is intended for use under the guidance of a healthcare provider. After proper training in subcutaneous injection technique, a patient may self-inject or the patient’s caregiver may administer HYMPAVZI, if a healthcare provider determines that it is appropriate. • Refer to the Instructions for Use for complete preparation and administration instructions. • Prior to subcutaneous administration, HYMPAVZI may be removed from the refrigerator and allowed to warm at room temperature [up to 86°F (30°C)] in the carton for 15 to 30 minutes protected from direct sunlight. Do not warm by using a heat source such as hot water or a microwave. After removal of HYMPAVZI from the refrigerator, use within 7 days or discard [see How Supplied/Storage and Handling (16) ] . • Administer HYMPAVZI by subcutaneous injection, once weekly, at any time of the day in the abdomen or front of thigh. Other injection sites are acceptable if required. Administration of HYMPAVZI in the back of upper arm (prefilled syringe only) or buttocks (prefilled pen only) should be performed by a caregiver or healthcare professional only. HYMPAVZI should not be administered into bony areas or areas where the skin is bruised, red, tender or hard, or areas where there are scars or stretch marks. HYMPAVZI should not be injected into a vein. Rotate the injection site with each new injection. • During treatment with HYMPAVZI, other medicinal products for subcutaneous administration should, preferably, be injected at different anatomical sites. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. HYMPAVZI is a clear and colorless to light yellow solution. Do not use if the solution is cloudy, dark yellow, or contains flakes or particles. 2.3 Changing to HYMPAVZI Changing from prophylactic factor replacement therapy to HYMPAVZI: Prior to initiation of HYMPAVZI, discontinue treatment with clotting factor concentrates (factor VIII or factor IX concentrates). HYMPAVZI can be initiated at any time after discontinuing clotting factor concentrates. No data are available in patients changing from non-factor-based hemophilia medicinal products to HYMPAVZI. 2.4 Guidance on Use with Breakthrough Bleed Treatments Factor VIII and factor IX products can be administered for the treatment of breakthrough bleeds in patients receiving HYMPAVZI. Do not use additional doses of HYMPAVZI to treat breakthrough bleeds. Healthcare providers should discuss with all patients and/or caregivers the dose and schedule of clotting factor concentrates to use, if required, while receiving HYMPAVZI prophylaxis, including using the lowest possible effective dose of clotting factor concentrate [see Warnings and Precautions (5.1) ] . Please refer to the Full Prescribing Information for the clotting factor concentrate being used. 2.5 Temporary Interruption for Surgery and Other Interventions Management in the Perioperative Setting HYMPAVZI has not been evaluated in the setting of major surgery. Patients have had minor surgical procedures without discontinuing HYMPAVZI prophylaxis in clinical studies. For major surgery, discontinue HYMPAVZI and initiate management per local standard of care with clotting factor concentrate and measures to manage the risk of venous thrombosis which can be elevated in the perioperative period. Consult the product information for the clotting factor concentrate for dosage guidelines in patients with hemophilia undergoing major surgery. Resumption of HYMPAVZI therapy should consider the overall clinical status of the patient, including the presence of post-surgical thromboembolic risk factors, use of other hemostatic products and other concomitant medications [see Dosage and Administration (2.1) ] . Management in Patients with Acute Severe Illness There is limited experience with the use of HYMPAVZI in patients with acute severe illness. Reasons to consider temporary dose interruption of HYMPAVZI include occurrence of acute severe illness (e.g., serious infection, sepsis, trauma) in which there may be increased activation of coagulation and which the healthcare provider considers could increase the risks associated with HYMPAVZI administration. Treatment of acute severe illness should be managed per local standard of care, and continued treatment with HYMPAVZI in this situation should be weighed against the potential risks involved. Resume HYMPAVZI therapy once patient has clinically recovered [see Dosage and Administration (2.1) ] . 2.6 Pregnancy Testing Verify that females of reproductive potential are not pregnant prior to initiating HYMPAVZI [see Warnings and Precautions (5.3) , Use in Specific Populations (8.1 , 8.3) ].

None. None. ( 4 )

The following clinically significant adverse reactions are described elsewhere in the labeling: • Thromboembolic Events [see Warnings and Precautions (5.1) ] • Hypersensitivity [see Warnings and Precautions (5.2) ] Adverse reactions reported in ≥3% of HYMPAVZI-treated patients were injection site reaction, headache, and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of HYMPAVZI was evaluated in adolescent and adult patients with severe hemophilia A or B without inhibitors (coagulation factor activity <1%) enrolled in the BASIS study [see Clinical Studies (14.1) ] . Patients (N = 116) received HYMPAVZI prophylaxis 300 mg loading dose followed by 150 mg every week starting at Day 8 administered subcutaneously. Among patients receiving HYMPAVZI, 97% were exposed for 6 months or longer and 75% were exposed for at least 1 year. A serious adverse reaction of peripheral swelling occurred in one patient. Table 1 summarizes the adverse reactions reported in ≥3% of patients who received HYMPAVZI prophylaxis. Table 1. Adverse Reactions Reported in ≥3% of Patients Treated with HYMPAVZI During BASIS trial 12-month active treatment phase Adverse Reaction Number of Patients n (%) (N = 116) Injection site reaction 11 (9) Headache 8 (7) Pruritus 4 (3) A serious adverse reaction of venous thrombosis occurred in 0.9% of patients (1/116) treated with HYMPAVZI in the open-label extension study [see Clinical Studies (14.1) ] .

Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) No clinically significant differences in standard measures of coagulation including activated partial thromboplastin time (aPTT) and prothrombin time (PT) were observed following marstacimab‑hncq therapy.

16.2 Recommended Storage and Handling • Store refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. • If needed, HYMPAVZI may be stored one time at room temperature [up to 86°F (30°C)] in its original carton to protect from light for up to 7 days. Once stored at room temperature, do not return to the refrigerator and discard after 7 days. • Do not freeze. • Do not shake.