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

Abstract

Objective:

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.

Data sources:

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.

Study selection and data extraction:

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.

Data synthesis:

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.

Conclusions:

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.