HYMPAVZI™ (marstacimab-hncq) 14 CLINICAL STUDIES

(marstacimab-hncq)

Prescribing Information

14 CLINICAL STUDIES

14.1 Hemophilia A without FVIII Inhibitors or Hemophilia B without FIX Inhibitors

The efficacy of HYMPAVZI was established in 116 adult and pediatric patients (aged 12 years and older and ≥35 kg) with severe hemophilia A without FVIII inhibitors or severe hemophilia B without FIX inhibitors enrolled in the BASIS study (NCT03938792), an open-label, multi-center, two-phase study. Severe hemophilia is defined as factor activity less than 1%. Patients with a history of coronary artery disease, venous or arterial thrombosis or ischemic disease were excluded from the study.

Following screening, patients entered a 6-month observation phase and were enrolled to two cohorts based on the factor replacement treatment they were receiving prior to study entry: on‑demand or routine prophylaxis. Patients who completed the observation phase were to receive 12 months of HYMPAVZI. Of the 116 patients who received HYMPAVZI, 33 patients were in the on‑demand treatment cohort and 83 were in the prophylactic treatment with FVIII or FIX cohort during the observation phase. Patients who completed the 12‑month BASIS study were eligible to enroll in an open-label extension study (NCT05145127).

Patients received an initial 300 mg loading dose of HYMPAVZI followed by maintenance doses of 150 mg of HYMPAVZI once weekly for 12 months. Dose escalation to 300 mg of HYMPAVZI once weekly was permitted after 6 months of treatment in patients weighing ≥50 kg and experiencing ≥2 breakthrough bleeds. Fourteen (12%) underwent dose escalation.

The mean annualized bleeding rates (ABRs) for treated bleeds were 39.86 and 7.90 in the observational phase for the on-demand and prophylaxis cohorts, respectively. All patients in the on-demand cohort had one or more target joints at study entry and 36% had 3 or more target joints at study entry. In the routine prophylaxis cohort, 57% of the patients had one or more target joints at study entry and 16% had 3 or more target joints at study entry.

The efficacy of HYMPAVZI for each cohort was based upon the ABR of treated bleeds during treatment with HYMPAVZI compared to ABR during the observational phase. Other objectives of the study included evaluation of HYMPAVZI prophylaxis on the incidences of spontaneous bleeds, joint bleeds, target joint bleeds and total bleeds.

Among the 116 patients treated with HYMPAVZI in the BASIS study, the mean age was 32 years (range 13 to 66); 19 patients were 12 to <18 years of age and all were male. Fifty-six (56) patients were White, 58 patients were Asian, 1 patient was Black or African American and 1 patient had race information unreported; 12 patients identified as Hispanic or Latino and 104 patients identified as not Hispanic or Latino. The patient population included 91 with hemophilia A and 25 with hemophilia B.

Patients with On-Demand Factor-Based Therapy in Observational Phase
Table 3 shows the efficacy results of HYMPAVZI prophylaxis compared with on-demand factor-based therapy. HYMPAVZI prophylaxis demonstrated superiority over on-demand factor-based therapy in incidences of treated bleeds, spontaneous bleeds, joint bleeds, total bleeds and target joint bleeds.

Table 3. Comparison of Annualized Bleeding Rate with HYMPAVZI Prophylaxis Versus On‑Demand Factor-Based Therapy in Patients ≥12 Years of Age without Factor VIII or Factor IX Inhibitors
• p-value for the null hypothesis that the ratio = 0.5.
• The estimated mean, ratio, and confidence intervals (CIs) for the ABR come from a negative binomial regression model.
• Bleed definitions adapted based on ISTH criteria: Treated bleeds = bleeds treated with FVIII or FIX; Total bleeds = bleeds treated and not treated with FVIII or FIX
• ABR = Annualized Bleeding Rate; CI = Confidence Interval; OD = On-Demand; OP = Observational Phase; ATP = Active Treatment Phase
Endpoints in the Order of Testing Hierarchy	On-Demand Factor-Based Therapy During 6-Month OP (N = 33)	HYMPAVZI Prophylaxis During 12-Month ATP (N = 33)
Treated Bleeds (Primary)
ABR, model-based (95% CI)	39.86 (33.05, 48.07)	3.20 (2.10, 4.88)
Ratio vs. OD (95% CI) p-value	0.080 (0.057, 0.113) <0.0001
Spontaneous Bleeds, Treated
ABR, model-based (95% CI)	32.63 (25.79, 41.28)	2.45 (1.62, 3.72)
Ratio vs. OD (95% CI) p-value	0.075 (0.053, 0.107) <0.0001
Joint Bleeds, Treated
ABR, model-based (95% CI)	34.52 (27.84, 42.79)	2.85 (1.82, 4.46)
Ratio vs. OD (95% CI) p-value	0.083 (0.057, 0.119) <0.0001
Total Bleeds, Treated & Untreated
ABR, model-based (95% CI)	49.97 (42.09, 59.32)	7.41 (5.10, 10.75)
Ratio vs. OD (95% CI) p-value	0.148 (0.111, 0.198) <0.0001
Target Joint Bleeds, Treated
ABR, model-based (95% CI)	24.38 (18.27, 32.53)	1.84 (1.07, 3.18)
Ratio vs. OD (95% CI) p-value	0.076 (0.048, 0.119) <0.0001

Patients with Routine Prophylactic Factor-Based Therapy
Table 4 shows the efficacy results of HYMPAVZI prophylaxis compared with routine prophylactic factor‑based therapy. HYMPAVZI prophylaxis demonstrated non-inferiority to routine prophylactic factor‑based therapy as measured by ABR of treated bleeds as well as incidences of spontaneous bleeds, joint bleeds, target joint bleeds and total bleeds.

Table 4. Comparison of Annualized Bleeding Rate with HYMPAVZI Prophylaxis Versus Previous Routine Factor-Based Prophylaxis in Patients ≥12 Years of Age without Factor VIII or Factor IX Inhibitors
• The protocol specified non-inferiority criterion (upper bound of the 95% CI for the difference) was 2.5 for treated bleeds, spontaneous bleeds, joint bleeds; 1.2 for target joint bleeds; 2.9 for total bleeds.
• The estimated mean, difference, and confidence intervals (CIs) for the ABR come from negative binomial regression model.
• Bleed definitions adapted based on ISTH criteria: Treated bleeds = bleeds treated with FVIII or FIX; Total bleeds = bleeds treated and not treated with FVIII or FIX
• ABR = Annualized Bleeding Rate; CI = Confidence Interval; OP = Observational Phase; ATP = Active Treatment Phase; RP = Routine Prophylaxis
Endpoints in the Order of Testing Hierarchy	Routine Factor-Based Prophylaxis During 6-Month OP (N = 83)	HYMPAVZI Prophylaxis During 12-Month ATP (N = 83)
Treated Bleeds (Primary)
ABR, model-based (95% CI)	7.90 (5.14, 10.66)	5.09 (3.40, 6.78)
Difference vs. RP (95% CI)	-2.81 (-5.42, -0.20)
Spontaneous Bleeds, Treated
ABR, model-based (95% CI)	5.89 (3.57, 8.22)	3.78 (2.25, 5.31)
Difference vs. RP (95% CI)	-2.11 (-4.26, 0.03)
Joint Bleeds, Treated
ABR, model-based (95% CI)	5.69 (3.36, 8.02)	4.13 (2.59, 5.67)
Difference vs. RP (95% CI)	-1.55 (-3.73, 0.62)
Total Bleeds, Treated & Untreated
ABR, model-based (95% CI)	8.90 (6.02, 11.77)	5.98 (4.14, 7.82)
Difference vs. RP (95% CI)	-2.91 (-5.66, -0.17)
Target Joint Bleeds, Treated
ABR, model-based (95% CI)	3.37 (1.60, 5.15)	2.51 (1.26, 3.76)
Difference vs. RP (95% CI)	-0.87 (-2.42, 0.69)

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. • 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. • 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. 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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