Sanofi recently announced that results of two clinical studies of their investigational therapy fitusiran were recently published in The Lancet and The Lancet Haematology journals. Both phase 3 trials were evaluating the efficacy and safety of fitusiran for the prophylactic treatment of adults and adolescents with hemophilia A or B. The enrolled participants, all of whom are 12 years of age and up, had been previously treated with existing factor replacement therapy or bypassing agent (BPA) prophylaxis.

Fitusiran is a subcutaneous therapy that uses small interfering RNA (siRNA) technology to target antithrombin (AT), a liver-generated clotting protein that plays a key role in the regulation of blood clots. siRNA molecules are segments of RNA (ribonucleic acid) that block or “silence” the activity of certain genes through RNA interference, a natural biological process common in plants and mammals. Fitusiran works by silencing the gene responsible for AT, which inhibits the protein’s anticoagulant function. This then compensates for the imbalance caused by deficiencies in other clotting proteins, such as factor VIII (hemophilia A) or factor IX (hemophilia B).

According to a new Sanofi press release, both studies compared once-monthly subcutaneous fitusiran prophylaxis (80mg) with on-demand/episodic use of clotting factor replacement in the ATLAS-A/B study, and on-demand/episodic use of a BPA in the ATLAS-INH study. Across both clinical studies, prophylactic treatment with fitusiran reduced annualized bleeding rates by 90% compared to the control arms, showing a “statistically significant and clinically meaningful” improvement in bleeding episodes when compared to on-demand treatments.

In the ATLAS-INH study published by The Lancet, 66% of participants with inhibitors (25 out of 38) receiving fitusiran 80mg monthly experienced zero bleeding episodes compared to 5% (1 out of 19) receiving an on-demand BPA after nine months of treatment. 

The ATLAS A/B study published in The Lancet Haematology showed 51% of participants without inhibitors (40 out of 79) who received fitusiran 80mg monthly prophylaxis experienced zero bleeds compared to 5% (2 out of 40) in the comparator group, receiving on-demand clotting factor replacement.

Sanofi is also currently investigating the efficacy and safety of fitusiran under a revised regimen which includes lower doses and less frequent dosing (as few as six subcutaneous injections per year), maintaining an antithrombin target range of 15-35% in all ongoing studies.

“Sanofi is committed to advancing the standard of care for all people with hemophilia through innovative science, providing consistent bleed protection while reducing treatment burden. We are entering a new era in hemophilia where, for the first time, people can choose therapies that meet their personal needs, stated Dietmar Berger, MD, PhD, Head of Global R&D ad interim and Chief Medical Officer at Sanofi. “These published data validate our science and add to a growing body of evidence supporting fitusiran’s potential to transform the treatment landscape. We look forward to sharing additional data on fitusiran later this year.”

Source: Sanofi press release dated April 4, 2023