Fitusiran prophylaxis reduced bleeds by 61% in people with hemophilia A or B, with or without inhibitors, compared to prior factor or bypassing agent prophylaxis

The study met the primary endpoint and demonstrated fitusiran prophylaxis significantly reduced bleeding episodes compared to prior factor or BPA prophylaxis.

Key findings in the Phase III ATLAS-PPX study include the following: i. The overall median annualized bleeding rate (ABR) was 0.0 for fitusiran prophylaxis, compared to a median ABR of 4.4 with prior prophylaxis. ii. Fitusiran prophylaxis resulted in a statistically significant reduction in estimated ABR of 61.1% (p=0.0008) versus factor or BPA prophylaxis. iii. 63.1% (n = 41) of adults and adolescents treated with fitusiran experienced zero treated bleeds compared to 16.9% (n = 11) with prior factor or BPA prophylaxis. iv. Median ABR for treated bleeds was 0.0 with fitusiran prophylaxis for both participants with and without inhibitors compared to 6.5 and 4.4 for participants with and without inhibitors, respectively, on prior prophylaxis. v. Of the 67 participants exposed to a least one dose of fitusiran, the most common adverse events (6 participants) were increased alanine aminotransferase, nasopharyngitis, and upper respiratory tract infection. vi. Consistent with the previously identified risk of fitusiran, suspected or confirmed thromboembolic events were reported in 2 participants (3.0%).

Collectively, these data add to a growing body of evidence, including results from the ATLAS A/B and ATLAS-INH Phase III studies, supporting fitusiran’s potential to transform treatment for all people with hemophilia. Hemophilia A and B are rare congenital bleeding disorders caused by a deficiency of factor VIII and IX, respectively, resulting in insufficient thrombin generation and ineffective clot formation further complicated in patients who develop inhibitors to their factor treatment. Sanofi is currently investigating the efficacy and safety of fitusiran under an amended protocol which includes lower doses and a less frequent dosing regimen maintaining an antithrombin target range of 15-35% in all ongoing studies. Fitusiran has the potential to provide prophylactic treatment for all people with hemophilia A or B, with or without inhibitors, with as few as six subcutaneous injections per year.