“Patients with severe haemophilia can develop inhibitors against factor VIII or IX, preventing factor replacement therapy from working,” said Dr Guy Young (University of Southern California, CA, USA). “A quarter of patients develops these inhibitors, leading to a worse prognosis. Novel agents are needed to protect these patients from bleeding events and arthropathy, and improve their quality of life. In addition, the current IV therapies need to be administered multiple times per week, resulting in venous access issues and poor adherence.”
Fitusiran is an investigational subcutaneous small interference RNA therapeutic targeting antithrombin. In the phase 3 ATLAS-INH trial (NCT03417102), patients with haemophilia A or B with inhibitors were randomised 2:1 to fitusiran therapy (80 mg, subcutaneous, once monthly) (n=38) or on-demand bypassing agents (BPA) (n=19). The primary endpoint was annualised bleeding rate (ABR) after 9 months. The median ABR for patients in the fitusiran arm was 0.0, compared with 16.8 in the BPA on-demand arm.
In addition, 65.8% of the patients treated with fitusiran displayed no bleeding events during the course of the study. In the BPA on-demand group, only 5% of the patients had no bleeding events. The Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) demonstrated a meaningful improvement in total score in patients treated with fitusiran (mean change -15.27), whereas patients in the BPA on-demand group did not show improvement in quality of life (mean change -0.42).
The safety analysis did not reveal new risks associated with fitusiran therapy. There were 11 patients with observed treatment-emergent adverse events (AEs) of special interest in the fitusiran group and 0 in the BPA on-demand group. The treatment-emergent AEs of special interest included 11 cases of mildly to moderately increased transaminases and 2 thromboembolic events. One patient in the fitusiran arm discontinued the study.
1. Young G, et al. Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI). PSS, ASH 2021 Scientific Sessions, 11–14 December.