The FDA has approved Pfizer's marstacimab-hncq (HYMPAVZI) for routine prophylaxis to prevent or reduce bleeding episodes in adults and adolescents aged 12 years and older with hemophilia A or B without inhibitors.
Marstacimab-hncq is the first anti-tissue factor pathway inhibitor (anti-TFPI) approved in the U.S. for hemophilia A or B treatment. It is also the first hemophilia medication approved for administration via a prefilled, auto-injector pen, offering a once-weekly subcutaneous dosing schedule.
Key Findings from Phase 3 BASIS Trial
The FDA approval is based on results from the Phase 3 BASIS trial (NCT03938792), which demonstrated:
- 35% reduction in annualized bleeding rate (ABR) compared to routine prophylaxis
- 92% reduction in ABR compared to on-demand treatment
- Consistent safety profile with Phase 1/2 results
- Most common adverse reactions (≥3% of patients): injection site reactions, headache, and pruritus
Mechanism of Action and Dosing
Marstacimab-hncq targets the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI). The approved dosing regimen includes:
- 300 mg subcutaneous loading dose
- 150 mg subcutaneous dose once weekly thereafter
- Potential dose escalation to 300 mg once weekly
Features of the New Treatment
This approval introduces:
- The first once-weekly subcutaneous prophylactic treatment for eligible hemophilia B patients
- The first hemophilia treatment administered via prefilled pen or syringe for both hemophilia A and B
- A different administration method compared to intravenous infusions
Safety Considerations
Health care providers should be aware of the following safety considerations:
- Potential increased risk of thromboembolic events
- Possibility of allergic reactions
- Importance of discussing factor VIII and factor IX product use for breakthrough bleeding
Ongoing Research
Additional studies are in progress:
- Inhibitor cohort of the BASIS trial (results expected Q3 2025)
- BASIS KIDS study in children 1 to <18 years old
The approval introduces a new treatment option for patients with hemophilia A or B without inhibitors. It represents the first anti-TFPI therapy and the first once-weekly subcutaneous treatment approved for this indication. As with all new treatments, ongoing research and long-term data will provide more information about its efficacy and safety profile in clinical practice.