Hympavzi Drug Information

• HYMPAVZI is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients 6 years of age and older with:
• Hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors, or
• Hemophilia B (congenital factor IX deficiency) with or 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 adults and pediatric patients 6 years of age and older with:
• Hemophilia B (congenital factor IX deficiency) with or without factor IX inhibitors.

Recommended Dosage in Adults and Pediatric Patients 12 Years of Age and Older For subcutaneous use only. The recommended dosage of HYMPAVZI for adults 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 In patients weighing greater than or equal to 50 kg, consider a dose adjustment to 300 mg subcutaneous injection weekly 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. 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).

Recommended Dosage in Pediatric Patients 6 to less than 12 Years of Age For subcutaneous use only.

Preparation and Administration • HYMPAVZI is intended for use under the guidance of a healthcare provider. After proper instruction in subcutaneous injection technique, a patient 12 years and older 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 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. • 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.

Changing to HYMPAVZI Changing from prophylactic factor replacement therapy or bypassing agents to HYMPAVZI: Prior to initiation of HYMPAVZI, discontinue treatment with clotting factor concentrates (factor VIII or factor IX concentrates) or bypassing agents (e.g., recombinant FVIIa or activated prothrombin complex concentrate ). HYMPAVZI can be initiated at any time after discontinuing clotting factor concentrates or bypassing agents. No data are available in patients changing from other non-factor-based hemophilia medicinal products to HYMPAVZI.

Guidance on Use with Breakthrough Bleed Treatments Factor VIII and factor IX products or bypassing agents (e.g., rFVIIa or aPCC) 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 the clotting factor concentrates or bypassing agents to use, if required, while receiving HYMPAVZI prophylaxis.

When treating breakthrough bleeds with factor VIII or factor IX products or with bypassing agents, the lowest effective dose according to the product prescribing information is recommended. Please refer to the Full Prescribing Information for the clotting factor concentrate or bypassing agent being used. For rFVIIa, a maximum dose of 90 mcg/kg body weight per dose and a maximum dosing frequency of every 2 hours is recommended.

For aPCC, a maximum dose of 100 units/kg body weight within 24 hours is recommended.

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, pause HYMPAVZI at least 7 days prior and initiate management per local standard of care with clotting factor concentrate or bypassing agent 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 or bypassing agent 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. 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.

Pregnancy Testing Verify that females of reproductive potential are not pregnant prior to initiating HYMPAVZI.

Immune Tolerance Induction

The safety and efficacy of HYMPAVZI in patients receiving ongoing Immune Tolerance Induction (ITI), a desensitization strategy for the eradication of inhibitors, have not been established, and no data are available. Careful assessment of the potential benefits and risks should be performed if continuation or initiation of HYMPAVZI during ITI is considered.

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 adults and pediatric patients 6 years of age and older with severe hemophilia A (FVIII <1%) or moderately severe to severe hemophilia B (FIX ≤2%) with and without inhibitors enrolled in the BASIS and BASIS KIDS studies. A total of 259 patients received the recommended HYMPAVZI prophylaxis loading dose followed by a weekly maintenance dose starting at Day 8 administered subcutaneously.

The median duration of exposure across the studies was 364 days (min, max: 14, 406 days). Table 1 summarizes the adverse reactions reported in ≥2% of patients in all age groups who received HYMPAVZI prophylaxis. Table 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.

Pregnancy Risk Summary Based on its mechanism of action, HYMPAVZI may cause fetal harm when administered to a pregnant woman. There are no available data on HYMPAVZI use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Female animal reproduction studies have not been conducted with HYMPAVZI.

Although there are no data on marstacimab‑hncq, monoclonal antibodies can be actively transported across the placenta, and marstacimab‑hncq may cause fetal harm. The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Pediatric Use The safety and effectiveness of HYMPAVZI to prevent or reduce the frequency of bleeding episodes in hemophilia A or B with and without inhibitors have been established in pediatric patients 6 years of age and older. Use of HYMPAVZI in pediatric patients for this indication is supported by evidence from two open‑label, multi‑center studies (BASIS and BASIS KIDS). These two studies treated 56 adolescents (12 to less than 18 years of age).

BASIS KIDS treated 68 children (6 to less than 12 years of age). Efficacy and adverse reaction profile were comparable between pediatric patients and adults. Differences observed in steady‑state pharmacokinetic (PK) exposures between pediatric patients and adults were mostly accounted for by body weight.

The safety and effectiveness of HYMPAVZI have not been established in pediatric patients younger than 6 years of age.

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for overdose management recommendations.