The U.S. Food and Drug Administration (FDA) has approved Pfizer's Hympavzi (marstacimab-hncq) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients (12 years and older) with hemophilia A (congenital factor VIII deficiency) or hemophilia B (congenital factor IX deficiency) without inhibitors. This approval marks a significant advancement in hemophilia treatment, offering a novel mechanism of action and a more convenient administration route. Hympavzi is the first and only anti-tissue factor pathway inhibitor (anti-TFPI) approved in the U.S. for hemophilia A or B.
Clinical Efficacy
The approval was supported by data from the Phase 3 BASIS trial (NCT03938792), which demonstrated Hympavzi's superiority in reducing bleeding episodes. In the study, Hympavzi reduced the annualized bleeding rate (ABR) for treated bleeds by 35% compared to routine prophylaxis (RP) and 92% compared to on-demand (OD) treatment after a 12-month active treatment period in patients with hemophilia A or B without inhibitors. The late-stage study included 116 hemophilia A or B patients.
Mechanism of Action
Hympavzi is an IgG1 monoclonal antibody that targets the Kunitz domain 2 of the tissue factor pathway inhibitor protein, which under healthy circumstances prevents blood clotting. Unlike existing treatments that replace missing clotting factors, Hympavzi enhances coagulation by reducing the activity of TFPI, a naturally occurring anticoagulant. This allows for the creation of more thrombin, an enzyme critical in blood clotting.
Administration and Dosage
Hympavzi offers a subcutaneous treatment option with a once-weekly dosing schedule and minimal preparation required for each individual administration. It is available as a pre-filled auto-injector pen, providing a more convenient and less burdensome treatment regimen compared to traditional intravenous infusions.
Impact on Patients
Hemophilia is a family of rare genetic blood diseases caused by a clotting factor deficiency (FVIII in hemophilia A, FIX in hemophilia B), impacting more than 800,000 people globally. The current standard of care often involves frequent, time-consuming intravenous infusions, which can significantly impact patients' quality of life. Hympavzi aims to reduce this treatment burden by offering a less frequent and more convenient subcutaneous administration.
Suchitra Acharya, director of the bleeding disorders program at Cohen Children's Medical Center, stated that 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.
Market and Financial Implications
Analysts expect sales of Hympavzi to reach $300 million by 2030. The drug's list price is $795,600 annually. This approval bolsters Pfizer's hemophilia portfolio, which also includes the gene therapy Beqvez, approved earlier this year for hemophilia B. Pfizer is also developing a gene therapy with Sangamo Therapeutics for the treatment of hemophilia A.
