Fitusiran Shows Promise as Long-Term Bleed Prevention Therapy in Hemophilia A and B

An interim analysis from the phase 3 ATLAS-OLE study reinforces the safety and efficacy of fitusiran, a subcutaneous investigational RNA interference (siRNA) therapy, for people with hemophilia A or B, with or without inhibitors.

The ATLAS-OLE study (NCT03754790), a global open-label extension trial, evaluated an antithrombin-based dose regimen (AT-DR) designed to rebalance hemostasis by reducing AT levels and enhancing thrombin generation. The study enrolled 213 participants as of June 2023, primarily continuing from previous phase 3 trials.

Fitusiran’s optimized dosing strategy—ranging from 20 to 80 mg at monthly or bi-monthly intervals—targeted AT activity levels between 15% to 35% to reduce thrombotic risk. Interim data revealed a median annualized bleeding rate (ABR) of 3.7, with over 70% of participants receiving injections only once every 2 months.

Integrated safety analyses of 286 participants confirmed that fitusiran AT-DR was well tolerated and no new safety concerns emerged. Efficacy analyses demonstrated a 71% reduction in mean ABR compared to on-demand clotting factor concentrates (P < .0001), and a 73% reduction vs on-demand bypassing agents (P = .0006). Additionally, fitusiran showed similar bleed control to prophylactic clotting factor therapy and outperformed bypassing agent prophylaxis.

“In ATLAS-OLE, AT-DR maintained clinically meaningful bleed protection, indicating that fitusiran is an effective treatment for people with hemophilia A or B, irrespective of inhibitor status,” said the authors.

Ongoing studies, including the ATLAS-NEO trial, aim to further explore fitusiran’s benefits and refine dosing strategies. These promising results support fitusiran as a potential paradigm shift in prophylactic hemophilia treatment.

Reference

Young G, Kavakli K, Klamroth R, et al. Safety and efficacy of a fitusiran antithrombin-based dose regimen in people with hemophilia A or B: the ATLAS-OLE study. Blood. 2025:blood.2024027008. doi:10.1182/blood.2024027008.