Abstract:

In recent years， to address the unmet needs in hemophilia treatment， significant research has led to unprecedented advances in pharmacotherapy， including the development of several innovative mechanism-based therapies that restore hemostatic balance by modulating thrombin generation in hemophilia patients with or without inhibitors. Among them， non-factor therapies involving hemostatic rebalancing mechanisms have achieved remarkable progress， with one of the key focuses in clinical development being anti-tissue factor pathway inhibitor （TFPI） therapy. TFPI is a key anticoagulant protein in the coagulation pathway that inhibits tissue factor （TF）-mediated initiation of coagulation. Blocking TFPI activity can enhance thrombin generation， providing a novel approach for hemophilia treatment. Notably， this mechanism applies to patients with hemophilia A or B and is theoretically effective for patients with or without inhibitors. As of June 2025， anti-TFPI agents that have entered clinical development or been approved for marketing internationally include concizumab， marstacimab， befovacimab， KN057， and MG1113. These agents inhibit TFPI activity through different antibody types， employing varying binding affinities or targeting distinct domains of TFPI. Studies on clinical trials across various phases have demonstrated that these drugs have good efficacy in reducing annual bleeding rates and improving patient prognosis. In addition， anti-TFPI drugs are administered subcutaneously， with dosing intervals up to one week， providing convenience for patients. Anti-TFPI therapy represents an important shift in the field of hemophilia management. However， it faces some challenges， including potential thrombotic risks and the current absence of suitable laboratory assays to monitor treatment efficacy.

Key words: Hemophilia, Anti-tissue factor pathway inhibitor, Thrombosis