Fitusiran in Hemophilia: A Novel Therapeutic Approach Targeting Antithrombin

Abstract

Fitusiran was FDA approved on March 28, 2025, for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or hemophilia B, with or without factor VIII or IX inhibitors (neutralizing antibodies). This article contains an overview of hemophilia and current treatment and prophylactic strategies, highlighting the key differences between fitusiran and other agents used for prophylaxis. It summarizes antithrombin’s role in the coagulation cascade and how fitusiran uses a novel mechanism as a small interfering RNA inhibitor that reduces expression of antithrombin. Pivotal clinical trials that led to its FDA approval are discussed, including dosing regimens, therapeutic drug monitoring, adverse effects, and clinical outcomes. This article provides in-depth information and clinical critique inclusive of and beyond the package insert guidance for advanced practitioners in hematology/oncology.