Mahlangu Johnny
Department of Molecular Medicine and Haematology, Faculty of Health Science, School of Pathology, University of the Witwatersrand and NHLS, Johannesburg, South Africa.
Expert Rev Hematol. 2025 Jul;18(7):521-527. doi: 10.1080/17474086.2025.2519002. Epub 2025 Jun 14.
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.
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.
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.
非因子疗法的开发是为了解决用于血友病出血管理的凝血因子浓缩物（CFC）的缺点。这些CFC未满足的需求包括高治疗负担、免疫原性、止血覆盖不一致、治疗效果差以及尽管进行了充分的预防性治疗仍有肌肉骨骼病变进展。已完成3期临床研究的抗组织因子途径抑制剂（抗TFPI）有康西珠单抗和马司他昔单抗。这些抗TFPI在血友病治疗手段中的作用仍不明确。
本综述批判性地评估了发表在PubMed、科学世界以及同行评审大会报告中的数据，以确定抗TFPI仅仅是补充当前的治疗选择，还是代表血友病治疗模式的颠覆性转变。它强调了替代疗法未满足的需求，并比较了抗TFPI与选定的FVIII和FIX产品的药代动力学、疗效和安全性数据。
随着血友病治疗目标不断演变，目前开发的抗TFPI的作用仍未完全明确。本综述全面总结了临床试验数据，表明抗TFPI并非旨在取代护理标准的CFC，而是为使用这些治疗药物治疗的血友病患者扩大治疗手段。
