Fitusiran Prophylaxis Shows Promise for Protection Against Bleeding for Patients With Hemophilia A or B

A phase 3, multicenter, open-label study published in Blood, evaluated the efficacy and safety of fitusiran—an investigational subcutaneous (SC) prophylactic small interfering RNA therapeutic used to target antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), regardless of inhibitor status—in males with hemophilia A or B. Researchers compared the fitusiran treatment regimen to the participants’ prior treatment of bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis.

The study was conducted at 35 sites and in 15 countries. Participants included males ≥12 years old who had severe hemophilia A or B, with or without inhibitors, who were receiving BPA or CFC. They were divided into two cohorts: (A) those with inhibitors and (B) those who did not have inhibitors. There was also a subcohort of group A that included those with inhibitors who were not responding adequately to BPA prophylaxis before enrolling in the study.

Study participants continued to receive BPA/CFC for six months. Following an onset period of one month where participants continued their BPA/CFC treatment for up to seven days, they switched to receiving 80 mg of fitusiran prophylaxis for seven months, once a month. Cohort A began receiving fitusiran prophylaxis directly after the screening period.

The researchers used the Haemophilia Quality of Life Questionnaire for Adults to assess health-related QoL (HRQoL) in participants aged ≥17 years. The primary endpoint of the study was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. The secondary endpoints were spontaneous ABR (AsBR) and joint ABR (AjBR). They also evaluated the safety and tolerability of the treatment.

Results from the study showed that fitusiran prophylaxis significantly reduced the mean ABR by 79.7% in participants with inhibitors vs BPA prophylaxis. In addition, there was a mean ABR reduction of 46.4% in the fitusiran vs CFC prophylaxis period for participants without inhibitors. The study also found that participants experienced significantly lower rates of spontaneous and joint bleeds, as well as reduction in target joint bleeds after the fitusiran prophylaxis treatment vs BPA/CFC prophylaxis. As a result, the participants had meaningful improvements in HRQoL, including requiring fewer IV infusions and lower consumption of BPAs/CFCs.

“These results suggest fitusiran prophylaxis may provide significant protection against bleeding while reducing the overall treatment and disease burden,” said the authors.

In terms of safety, the adverse events experienced by the participants were generally consistent with previous studies; these included increased thrombosis, transaminases, cholecystitis, and symptomatic cholelithiasis. Overall, fitusiran prophylaxis was tolerated well among the study’s participants.

“Fitusiran might help address unmet needs of achieving consistent bleed protection, less burdensome prophylaxis with a convenient dosing regimen, and improved QoL in PwH,” concluded the authors.

Reference

Kenet G, Nolan B, Zulfikar B, et al. Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial. Blood. 2024;143(22):2256-2269. doi:10.1182/blood.2023021864