Hympavzi

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).

Preparation and Administration

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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.

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Refer to the Instructions for Use for complete preparation and administration instructions.

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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)].

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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.

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During treatment with HYMPAVZI, other medicinal products for subcutaneous administration should, preferably, be injected at different anatomical sites.

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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 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.

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.

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)].

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)].

Pregnancy

Risk Summary
Based on its mechanism of action, HYMPAVZI may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. 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 2% to 4% and 15% to 20%, respectively.

Lactation

Risk Summary
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.

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

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

Females and Males of Reproductive Potential

HYMPAVZI may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating HYMPAVZI treatment.

Contraception
Females
Advise female patients of reproductive potential to use effective contraception during treatment with HYMPAVZI and for 2 months after the last dose.

Pediatric Use

The safety and effectiveness of HYMPAVZI to prevent or reduce the frequency of bleeding episodes in hemophilia A or B without inhibitors have been established in pediatric patients aged 12 years and older [see Clinical Studies (14.1)]. Use of HYMPAVZI for this indication is supported by evidence from an open‑label, multi‑center phase 3 study in 19 adolescents and 97 adults with hemophilia without inhibitors.

The safety and effectiveness of HYMPAVZI have not been established in pediatric patients younger than 12 years old.

Geriatric Use

One patient 65 years of age and older was enrolled in the clinical studies for hemophilia A or B without inhibitors [see Clinical Studies (14.1)]. Clinical studies of HYMPAVZI did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.

Thromboembolic Events

HYMPAVZI is a tissue factor pathway inhibitor (TFPI) antagonist, and may increase the risk of thromboembolic complications. Venous thrombotic events were reported in clinical studies with HYMPAVZI [see Adverse Reactions (6.1)].

Patients with independent risk factors for thromboembolic events may be at increased risk of thromboembolic events with use of HYMPAVZI.

HYMPAVZI has not been studied in patients with a history of previous thromboembolic events [see Clinical Studies (14.1)]. Consider the benefit and risk of using HYMPAVZI in patients with known risk factors for thromboembolism.

Interrupt HYMPAVZI prophylaxis if diagnostic findings consistent with thromboembolism occur and manage as clinically indicated.

If factor VIII or factor IX products are indicated in a patient receiving HYMPAVZI prophylaxis, the minimum effective dose of factor VIII or factor IX according to the product label is recommended [see Dosage and Administration (2.4)].

Hypersensitivity

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

Embryofetal Toxicity

Based on its mechanism of action, HYMPAVZI may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with HYMPAVZI and for 2 months after the last dose [see Use in Specific Populations (8.1, 8.3)].