(marstacimab-hncq)

Prescribing Information
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12 CLINICAL PHARMACOLOGY

12 CLINICAL PHARMACOLOGY

  

12.1 Mechanism of Action

Marstacimab‑hncq is a human monoclonal IgG1 antibody directed against the Kunitz domain 2 (K2) of TFPI to neutralize TFPI activity and enhance coagulation. TFPI is the primary inhibitor of the extrinsic coagulation cascade and negatively regulates thrombin generation within the extrinsic pathway of coagulation by inactivating the protease functions of FXa/FVIIa/TF complex. TFPI binds to and inhibits the factor Xa active site via its second Kunitz inhibitor domain (K2).

12.2 Pharmacodynamics

Marstacimab‑hncq causes an increase in total TFPI (comprised of free TFPI and TFPI bound to marstacimab) and downstream biomarkers of thrombin generation such as prothrombin fragments 1+2, peak thrombin, and D‑Dimer in patients with hemophilia. These changes were observed and persisted over a 7-day period following a single subcutaneous dose and were reversible after treatment discontinuation.

12.3 Pharmacokinetics

Estimated mean marstacimab‑hncq Cmin,ss, Cmax,ss, and Cavg,ss for adults and adolescents weighing at least 35 kg following marstacimab‑hncq 150 mg subcutaneous once-weekly administration are shown in Table 2. Marstacimab‑hncq area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) increase in a greater than dose-proportional manner over the dose range of 100 mg to 450 mg (0.67 to 3 times the approved recommended dosage).

Mean steady-state accumulation ratio for marstacimab‑hncq is approximately 4 to 5. Marstacimab‑hncq steady‑state concentrations are achieved by approximately 60 days (8th or 9th subcutaneous dose) when administered once weekly.

Table 2. Steady-State Marstacimab‑hncq Plasma Concentrations Following Once-Weekly Subcutaneous Administration of 150 mg (with a Loading Dose of 300 mg Subcutaneous)
•     Data are presented as arithmetic mean (%CV).
•     Cmin,ss = minimum plasma concentration at steady state; Cmax,ss = maximum plasma concentration at steady state; Cavg,ss = average plasma concentration at steady state.

Parameter

Adults

Adolescents

Cmin,ss (mcg/mL)

13.7 (90.4%)

27.3 (53.2%)

Cmax,ss (mcg/mL)

17.9 (77.5%)

34.7 (48.5%)

Cavg,ss (mcg/mL)

16.5 (81.2%)

32.1 (49.5%)

Absorption
Bioavailability of marstacimab‑hncq following subcutaneous administration is approximately 71%. Median Tmax ranges from 23 to 59 hours following multiple subcutaneous administrations of marstacimab‑hncq to patients with hemophilia. No clinically significant differences were seen in marstacimab‑hncq bioavailability when administered subcutaneously in the arm, thigh or abdomen.

Distribution
Marstacimab‑hncq steady-state apparent volume of distribution is 8.6 L in patients with hemophilia.

Elimination
Marstacimab-hncq is cleared via linear and non-linear mechanisms. Marstacimab‑hncq exhibited non‑linear pharmacokinetics due to target-mediated drug disposition (TMDD) which occurs when it forms marstacimab‑hncq/TFPI complex. Once the target becomes saturated, linear pathway (i.e., catabolism) dominates.

Based on population pharmacokinetic analysis, 90% of marstacimab is expected to be eliminated by the end of approximately 1 month after the last dose (median time for 50% of drug to be eliminated is approximately 7 to 10 days).

Metabolism
Marstacimab‑hncq is expected to be metabolized into small peptides and amino acids by catabolic pathways in the same manner as endogenous IgG.

Specific Populations
No clinically significant differences in pharmacokinetics of marstacimab‑hncq were observed based on race, hemophilia type (A and B), mild renal impairment (eGFR of 60 to 89 mL/min/1.73 m2), and mild hepatic impairment (total bilirubin >1× to ≤1.5× ULN). The effects of geriatric age (>65 years), moderate to severe renal (eGFR <59 mL/min/1.73 m2) and moderate to severe hepatic (Child Pugh class B and C) impairment on marstacimab‑hncq pharmacokinetics are unknown.

Body Weight
Body weight was a significant covariate impacting the pharmacokinetics of marstacimab‑hncq. Marstacimab‑hncq exposures over the body weight range of 35 to 120 kg show a trend for increase in exposure with decrease in body weight. However, dose adjustment based on body weight is not required.

Pediatric Patients
Marstacimab‑hncq clearance (CL) was 29% lower in adolescents (12 to <18 years of age) compared to adults (18 years and older). No clinically significant difference in adolescent marstacimab‑hncq CL (L/hr/kg) compared to adults was observed after adjusting for body weight.

12.6 Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and the specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the studies described below with the incidence of ADA in other studies, including those of marstacimab‑hncq or of other marstacimab products.

During the 12-month active treatment phase in the BASIS study, 23 of the 116 (19.8%) ADA‑evaluable marstacimab‑hncq‑treated patients developed ADAs. Among the 23 patients who tested positive for ADA, 6 patients (26%) developed neutralizing antibodies (NAbs) against marstacimab‑hncq. Subjects who received marstacimab‑hncq and developed anti-marstacimab-hncq antibodies had reduced marstacimab-hncq steady‑state concentrations, geometric mean decrease in the range of 24% to 50%, compared to those who did not develop anti‑marstacimab‑hncq antibodies through the course of the treatment period.

There was no identified clinically significant effect of ADAs, including NAbs, on safety or efficacy of marstacimab‑hncq over the treatment duration of 12 months.

Medication Guide

MEDICATION GUIDE

     

This Patient Information has been approved by the U.S. Food and Drug Administration.          Revised: 09/2025

PATIENT INFORMATION

HYMPAVZI (him-PAV-zee)

(marstacimab-hncq)

injection, for subcutaneous use

Important information: Before you start using HYMPAVZI, it is very important to talk to your healthcare provider about using factor VIII and factor IX products (products that help blood clot but work in a different way than HYMPAVZI). You may need to use factor VIII or factor IX medicines to treat episodes of breakthrough bleeding during treatment with HYMPAVZI. Carefully follow your healthcare provider’s instructions regarding when to use factor VIII or factor IX medicines and the prescribed dose during your treatment with HYMPAVZI.

What is HYMPAVZI?

HYMPAVZI is a prescription medicine used regularly to prevent or reduce the frequency of bleeding episodes in adults and children 12 years of age and older with hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors.

It is not known if HYMPAVZI is safe and effective in children younger than 12 years old.

Before using HYMPAVZI, tell your healthcare provider about all of your medical conditions, including if you:

•
have a planned surgery. Your healthcare provider may stop treatment with HYMPAVZI before your surgery. Talk to your healthcare provider about when to stop using HYMPAVZI and when to start it again if you have a planned surgery.
•
have a severe short-term (acute) illness such as an infection or injury.
•
have been told that you have a risk for blood clots.
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are pregnant or plan to become pregnant. HYMPAVZI may harm your unborn baby.
 
Females who are able to become pregnant:
o
Your healthcare provider will do a pregnancy test before you start your treatment with HYMPAVZI.
o
You should use effective birth control (contraception) during treatment with HYMPAVZI and for 2 months after the last dose of HYMPAVZI.
o
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with HYMPAVZI.
•
are breastfeeding or plan to breastfeed. It is not known if HYMPAVZI passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription medicines, over‑the‑counter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I use HYMPAVZI?

See the detailed “Instructions for Use” that comes with your HYMPAVZI for information on how to inject a dose of HYMPAVZI, and how to properly throw away (dispose of) used HYMPAVZI prefilled syringe or HYMPAVZI prefilled pen.

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Use HYMPAVZI exactly as prescribed by your healthcare provider.
•
Your healthcare provider will provide instructions for stopping (discontinuing) your current treatment when switching from factor- or non-factor-based medicines to HYMPAVZI.
•
HYMPAVZI is given as an injection under your skin (subcutaneous injection) by you or your caregiver.
•
Your healthcare provider should show you or your caregiver how to inject HYMPAVZI before you inject yourself for the first time.
•
Do not attempt to inject yourself or another person unless you have been taught how to do so by a healthcare provider.
•
Your first dose (loading dose) of HYMPAVZI is 300 mg (two 150 mg injections). Then you will inject a weekly (maintenance) dose as prescribed by your healthcare provider.
•
Inject HYMPAVZI 1 time a week on the same day each week. Inject HYMPAVZI at any time of day.
•
Your healthcare provider will provide information on the treatment of breakthrough bleeding during your treatment with HYMPAVZI. Do not use HYMPAVZI to treat breakthrough bleeding.
•
If you miss a maintenance dose of 150 mg of HYMPAVZI:
o
Give the dose as soon as possible before the next scheduled dose, and then continue with your usual 150 mg weekly dosing schedule. You may inject your next dose at your regularly scheduled time or continue dosing based on the new day you injected your missed dose. In case you are not sure when to inject HYMPAVZI, call your healthcare provider.
o
If more than 13 days have passed since your last dose was given, call your healthcare provider right away for dosing instructions.
•
If you miss 1 or more doses of maintenance dose of 300 mg of HYMPAVZI:
o
Give a dose as soon as possible, and then continue with your 300 mg weekly dosing schedule. You may inject your next dose at your regularly scheduled time or continue dosing based on the new day you injected your missed dose. In case you are not sure when to inject HYMPAVZI, call your healthcare provider.

What are the possible side effects of HYMPAVZI?

HYMPAVZI may cause serious side effects, including:

•
blood clots (thromboembolic events). HYMPAVZI may increase the risk for your blood to clot in blood vessels in your arm, leg, lung, or head and can be life-threatening. Blood clots have happened in people using HYMPAVZI. You may have an increased risk of blood clots if you have certain risk factors. Stop using HYMPAVZI and get medical help right away if you develop any of these signs or symptoms of blood clots:
o
swelling or pain in arms or legs
o
redness or discoloration in your arms or legs
o
shortness of breath
o
pain in chest or upper back
o
fast heart rate
o
cough up blood
o
feel faint
o
headache
o
numbness in your face
o
eye pain or swelling
o
trouble seeing
•
allergic reactions. HYMPAVZI may cause allergic reactions, including rash and itching. Stop using HYMPAVZI and get medical help right away if you develop any of the following symptoms of a severe allergic reaction:
o
swelling of your face, lips, mouth, or tongue
o
trouble breathing
o
wheezing
o
dizziness or fainting
o
fast heartbeat or pounding in your chest
o
sweating

The most common side effects of HYMPAVZI include:

•
swelling, hardening, redness, bruising, and pain at injection site
•
headache
•
itching

These are not all of the possible side effects of HYMPAVZI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store HYMPAVZI?

•
Store HYMPAVZI in a refrigerator at 36°F to 46°F (2°C to 8°C).
•
Store HYMPAVZI 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 for up to 7 days. Do not return HYMPAVZI to the refrigerator after storing at room temperature.
•
Throw away (dispose of) HYMPAVZI that has been left out of the refrigerator for more than 7 days.
•
Do not freeze HYMPAVZI.
•
Do not shake HYMPAVZI.

Keep HYMPAVZI and all medicines out of the reach of children.

General information about the safe and effective use of HYMPAVZI.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use HYMPAVZI for a condition for which it was not prescribed. Do not give HYMPAVZI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about HYMPAVZI that is written for health professionals.

What are the ingredients in HYMPAVZI?

Active ingredient: marstacimab‑hncq

Inactive ingredients: edetate disodium, histidine, L-histidine monohydrochloride, polysorbate 80, sucrose, and water for injection

This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

Pfizer logo
US License No. 2001
Distributed by: Pfizer Labs, Division of Pfizer Inc., New York, NY 10001
LAB-1575-2.0
For more information, go to website www.HYMPAVZI.com or call 1-800-438-1985.

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