The U.S. Food and Drug Administration (FDA) has approved HYMPAVZI™ (marstacimab-hncq), developed by Pfizer Inc., for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients (12 years and older) with hemophilia A (congenital factor VIII deficiency) without factor VIII inhibitors, or hemophilia B (congenital factor IX deficiency) without factor IX inhibitors. This approval marks a significant advancement in hemophilia treatment, offering a novel mechanism of action and a convenient administration route.
Novel Anti-TFPI Mechanism
HYMPAVZI is the first and only anti-tissue factor pathway inhibitor (anti-TFPI) approved in the U.S. for hemophilia A or B. Unlike traditional factor replacement therapies, HYMPAVZI works by rebalancing hemostasis. It targets the Kunitz 2 domain of TFPI, a natural anticoagulant protein, to promote blood clot formation. This mechanism increases thrombin generation, which is critical for effective blood clotting.
Clinical Trial Efficacy
The approval was supported by results from the Phase 3 BASIS trial (NCT03938792), a global, open-label, multicenter study. The study included 116 participants with severe hemophilia A or moderately severe to severe hemophilia B, both without inhibitors. Participants were treated with HYMPAVZI during a 12-month active treatment period (ATP) following a six-month observational period on either routine prophylaxis (RP) or on-demand (OD) treatment with FVIII or FIX.
Results showed that HYMPAVZI reduced the annualized bleeding rate (ABR) for treated bleeds by 35% compared to RP and by 92% compared to OD treatment. Specifically, in the OD group, HYMPAVZI demonstrated superiority (p<0.0001) across all bleeding-related secondary endpoints, including spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds. In the RP group, HYMPAVZI demonstrated non-inferiority in these secondary efficacy endpoints.
Convenient Subcutaneous Administration
HYMPAVZI is the first hemophilia medicine approved in the U.S. to be administered via a pre-filled, auto-injector pen. It offers a once-weekly subcutaneous treatment option, reducing the burden of frequent intravenous infusions. This is particularly beneficial for patients who find the time-consuming nature of traditional prophylaxis challenging. A survey indicated that nearly one-third of patients on prophylaxis, even with high compliance, cited the time commitment as a significant burden.
Safety Profile and Considerations
The safety profile of HYMPAVZI was consistent with Phase 1/2 results. The most commonly reported adverse reactions (≥3% of patients) in the BASIS study were injection site reactions, headache, and pruritus. However, the drug carries warnings and precautions about potential thromboembolic events, hypersensitivity, and embryofetal toxicity. Patients should be monitored for signs and symptoms of blood clots, and females of reproductive potential should use effective contraception during treatment.
Impact on Hemophilia Care
Hemophilia is a rare genetic blood disease affecting more than 800,000 people globally. It results from a deficiency in clotting factors (FVIII in hemophilia A, FIX in hemophilia B), leading to impaired blood clotting and an increased risk of bleeding. The introduction of HYMPAVZI provides a new treatment option that addresses some of the ongoing challenges faced by people with hemophilia A and B, potentially improving their quality of life and reducing the burden of care.
