The U.S. Food and Drug Administration (FDA) has approved Hympavzi (marstacimab-hncq), developed by Pfizer, for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients 12 years of age and older with hemophilia A without factor VIII inhibitors, or hemophilia B without factor IX inhibitors.
This approval marks a significant advancement in hemophilia treatment, as Hympavzi is the first and only anti-tissue factor pathway inhibitor (anti-TFPI) approved in the U.S. for hemophilia A or B. It is also the first hemophilia medicine in the U.S. to be administered via a pre-filled, auto-injector pen, offering a subcutaneous treatment option with a once-weekly dosing schedule.
Novel Mechanism of Action
Hympavzi's unique mechanism of action sets it apart from traditional hemophilia treatments. Unlike factor replacement therapies that increase the amount of clotting factor in the body, Hympavzi works by reducing the activity of tissue factor pathway inhibitor (TFPI), a naturally occurring anticoagulation protein. By inhibiting TFPI, Hympavzi increases the generation of thrombin, an enzyme critical for blood clotting, thereby reducing the frequency of bleeding episodes.
Clinical Trial Data
The FDA's approval was based on data from the Phase 3 BASIS trial (NCT03938792), a global, open-label, multi-center study that evaluated the efficacy and safety of Hympavzi in adolescent and adult participants with severe hemophilia A or moderately severe to severe hemophilia B, with or without inhibitors. The study included 116 people living with hemophilia without inhibitors who were treated with HYMPAVZI during a 12-month active treatment period (ATP) versus an RP and OD intravenous regimen with FVIII or FIX, administered as part of usual care in a six-month observational period.
The results demonstrated that Hympavzi reduced the annualized bleeding rate (ABR) for treated bleeds by 35% and 92% after a 12-month ATP compared to routine prophylaxis (RP) and on-demand (OD) treatment, respectively, in patients with hemophilia A or B without inhibitors. In the OD group, superiority (p<0.0001) of HYMPAVZI was demonstrated across all bleeding-related secondary endpoints – spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds. In the RP group, HYMPAVZI demonstrated non-inferiority to these secondary efficacy endpoints.
Expert Commentary
Suchitra S. Acharya, M.D., Director of the Hemostasis and Thrombosis Center Northwell Health, Program Head, Bleeding Disorders and Thrombosis Program, Cohen Children’s Medical Center, stated, “The approval of HYMPAVZI is a meaningful advancement for people living with hemophilia A or B without inhibitors for bleed prevention, with a generally manageable safety profile and a straightforward once-weekly subcutaneous administration. HYMPAVZI aims to reduce the current treatment burden by meeting an important need for these patients, including many who have required frequent, time-consuming intravenous treatment infusion regimens.”
Safety and Tolerability
The safety profile of Hympavzi was consistent with Phase 1/2 results, and treatment was generally well-tolerated. The most commonly reported adverse reactions (≥3% of patients) in the study were injection site reactions, headache, and pruritus.
Addressing Unmet Needs
Hemophilia is a rare genetic blood disease caused by a deficiency in clotting factors, affecting more than 800,000 people globally. Patients with hemophilia experience prolonged bleeding after injury or surgery, as well as spontaneous bleeding in muscles, joints, and organs. The approval of Hympavzi offers a new treatment option that can reduce the frequency of bleeding episodes and improve the quality of life for people living with hemophilia A and B without inhibitors.
Future Directions
The inhibitor cohort of the BASIS trial is ongoing, with results expected in the third quarter of 2025. Pfizer is also conducting BASIS KIDS, an open-label study investigating the safety and efficacy of marstacimab in children 1 to <18 years of age with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors.
With this approval, Pfizer now offers three distinct classes of hemophilia medicines – an anti-TFPI, gene therapy, and recombinant factor treatments – to meet the unique treatment needs of a wide range of patients.
