Novel Non-Factor Therapies in Hemophilia: Insights from Phase 3 Trials

Recent advances in hemophilia treatment include first-in-class non-factor therapies with unique mechanisms of action. Fitusiran, an antithrombin-lowering siRNA approved in 2024, works by degrading antithrombin to enhance clot formation, offering prophylaxis for patients with hemophilia A or B, including those with inhibitors. Phase 3 trials demonstrated meaningful reductions in bleeding episodes and a favorable safety profile, supporting its role as a transformative prophylactic option. Similarly, concizumab and marstacimab—anti-TFPI antibodies approved the same year—target the tissue factor pathway inhibitor to restore hemostatic balance. Phase 3 data showed effective bleed prevention across adults and adolescents, highlighting the clinical potential of TFPI modulation. These trials collectively expand understanding of non-factor approaches, providing alternatives for patients with unmet needs and offering opportunities for more convenient, tailored prophylactic strategies that may reduce treatment burden and improve quality of life.