Anti-tissue factor pathway inhibitors for hemophilia: are these treatments the answer to overcoming current treatment limitations?

Authors: Mahlangu, J

Affiliations: Department of Molecular Medicine and Haematology, Faculty of Health Science, School of Pathology, University of the Witwatersrand and NHLS, Johannesburg, South Africa.

Publication: Expert Review of Hematology; 2025

ABSTRACT: INTRODUCTION: Non-factor therapies were developed to address the shortcomings of clotting factor concentrates (CFCs) used for hemophilia bleed management. These CFC unmet needs include high treatment burden, immunogenicity, inconsistent hemostatic cover, poor treatment outcomes, and musculoskeletal progression despite adequate prophylactic treatment. Anti-tissue factor pathway inhibitors (anti-TFPIs) that have completed Phase 3 clinical studies are concizumab and marstacimab. The role of these anti-TFPIs in the hemophilia treatment armamentarium remains unclear. AREAS COVERED: This review critically appraises data published in PubMed, World of Science, and peer-reviewed congress presentations to determine whether anti-TFPIs merely supplement current treatment options or represent a disruptive shift in the treatment paradigm for hemophilia. It underscores the unmet needs of replacement therapies and compares the pharmacokinetic, efficacy, and safety data of anti-TFPIs and selected FVIII and FIX products. EXPERT OPINION: As hemophilia treatment goals continue to evolve, the role of currently developed anti-TFPIs is still not fully defined. This review comprehensively summarizes the clinical trial data, which shows that anti-TFPIs are not intended to replace the standard of care CFCs but to expand the therapeutic arsenal for patients with hemophilia treated with these therapeutic agents.