Fitusiran Shows Sustained Bleed Control and Safety With AT-Guided Dosing in Hemophilia

Findings from a phase 2 open-label extension study suggest that fitusiran, a small interfering RNA (siRNA) therapy targeting antithrombin (AT), offers sustained bleeding control and quality of life improvements in people with moderate or severe hemophilia A or B, with or without inhibitors.

In this long-term study (median exposure, 4.1 years), 34 male participants received monthly subcutaneous fitusiran under either an original fixed-dose regimen (50 or 80 mg) or a modified AT-based dosing strategy targeting 15% to 35% AT activity levels. The AT-based regimen was introduced following thrombotic events in the broader clinical program, prompting a risk mitigation strategy.

Fitusiran maintained low annualized bleed rates (median ABR: 0.70 on the original regimen; 0.87 on the AT-based regimen), and no thrombotic events occurred after the AT-based dosing was implemented. Liver enzyme elevations and biliary events were also less frequent under the revised regimen. Additionally, participants reported improvements in health-related quality of life and demonstrated successful bleed control during surgical procedures.

Overall, the findings support the long-term safety and efficacy of fitusiran as prophylaxis in hemophilia A and B, reinforcing its potential as a nonfactor treatment option that may help rebalance hemostasis while mitigating thrombotic risk through tailored AT level management.

Reference

Pipe SW, Lissitchkov T, Georgiev P, et al. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025;9(5):1147-1158. doi:10.1182/bloodadvances.2024013900