Sanofi recently shared new clinical trial updates for their investigational hemophilia therapy fitusiran. The Phase 3 ATLAS-PPX study is evaluating the efficacy and safety of fitusiran (80 mg) when administered prophylactically (once per month) to adults and adolescents with severe hemophilia A or B. The 80 participants enrolled in the trial, 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).
The updates, presented on July 10th at the International Society on Thrombosis and Haemostasis (ISTH) Congress in London, showed positive results when fitusiran was compared to previous prophylactic therapy. According to a Sanofi press release, the overall median annualized bleeding rate (ABR) was 0.0 for fitusiran prophylaxis, compared to a median ABR of 4.4 with prior prophylaxis. Fitusiran prophylaxis resulted in a “statistically significant” reduction in estimated ABR of 61.1% versus factor or BPA prophylaxis. In addition, 63.1% of adults and adolescents treated with fitusiran experienced zero treated bleeds compared to 16.9% with prior factor or BPA prophylaxis.
In terms of safety, of the 67 participants exposed to a least one dose of fitusiran, the most common adverse events were increased liver enzymes, cold symptoms, and upper respiratory tract infection. In addition, suspected or confirmed thromboembolic events were reported in two participants (3%) – this was reportedly consistent with the previously identified risk of fitusiran.
“These positive data support fitusiran’s potential to transform prophylaxis treatment for people with hemophilia A or B, with or without inhibitors, with a median annual bleed rate of zero across all patient populations, said Dietmar Berger MD, PhD, Global Head of Development and Chief Medical Officer at Sanofi. “Moreover, we are excited to continue to explore fitusiran under an amended protocol that focuses on dose optimization, including lower doses and less frequent dosing regimens, with the potential for as few as six injections per year.”
Additional data relevant to the fitusiran clinical trial program, delivered at the Congress via oral/poster presentations, may currently be viewed on the ISTH website:
Consumption of On-demand Factor Concentrates and Bypassing Agents for Management of Breakthrough Bleeds with Fitusiran Prophylaxis in People with Haemophilia A or B: An Analysis of Two Phase 3 Studies
Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin: Analysis of Antithrombin Levels and Thrombin Generation from a Phase 3 Study in People with Hemophilia A or B Without inhibitors
Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin: Analysis of Antithrombin Levels and Thrombin Generation from a Phase 3 Study in People with Hemophilia A or B With Inhibitors
Source: Sanofi press release dated July 10, 2022