Fitusiran: A Novel Antithrombin-Targeting Therapy for Hemophilia A and B, With or Without Inhibitors

The objective of the study is to critically review the literature about clinical evidence on the efficacy and safety of fitusiran among patients with hemophilia A or B.

A targeted search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was performed from inception through November 2025 using the terms fitusiran, antithrombin, RNA interference, siRNA, and hemophilia A or B.

Eligible studies were randomized controlled trials across all phases enrolling patients with hemophilia A or B. The review incorporated 2 phase 1 studies, 1 phase 2 study, and 4 phase 3 trials.

Fitusiran prophylaxis reduced annualized bleeding rates by about 70% to 90% compared with on-demand therapy or previous prophylaxis using bypassing agents, and by up to 50% compared with prior prophylaxis with clotting factor concentrates. Between 50% and 65% of participants experienced no bleeds requiring treatment. Health-related quality of life improved, with mean reductions in Hemophilia-specific Quality of Life Questionnaire for Adults (Haem-A-QoL) scores ranging from -4.6 to -12.3. Safety evaluations showed aminotransferase elevations in 19% to 25%, gallbladder events in 13% to 15%, and thrombotic events in ≤5% of patients, primarily associated with low antithrombin levels or excessive factor use. Long-term extension studies confirmed sustained bleed protection and safety with antithrombin-guided dosing.Relevance to patient care and clinical practice in comparison to existing drugs:Fitusiran is a subcutaneous nonfactor prophylactic treatment that lowers antithrombin to rebalance coagulation with or without inhibitors in patients with hemophilia A and B. It is administered every 2 months, and associated with fewer bleeds, and improved quality of life compared with standard of care.

Fitusiran expands prophylactic options for hemophilia A and B, providing sustained bleed protection with infrequent dosing. Integration into practice requires monitoring of antithrombin activity to mitigate thrombotic or bleeding risk, and liver and gallbladder functions for safety.