Fitusiran Achieves Phase 3 Clinical Trial Endpoints in Hemophilia with 65.8% of Patients Reporting Zero Annualized Bleeding Rate

Recently, Sanofi announced that it will present positive results from the Phase 3 clinical trial of fitusiran, an RNAi therapy jointly developed with Alnylam, for the treatment of hemophilia A and hemophilia B, at this year’s American Society of Hematology (ASH) Annual Meeting.

Hemophilia A and Hemophilia B are coagulation disorders caused by the lack of clotting factor VIII and IX, respectively. Fitusiran is an RNAi therapy targeting antithrombin. It works by binding to the RNA that expresses antithrombin, reducing its production, thereby restoring the balance between clotting factors and anticoagulant factors, which helps reduce bleeding events in hemophilia patients. This innovative therapy requires only once-monthly subcutaneous injections, offering significant convenience for patients in managing bleeding risks compared to conventional prophylactic clotting factor injections. Moreover, it can treat both Hemophilia A and B patients, regardless of whether they express inhibitors against exogenous clotting factors.

▲Mechanism of Action of Fitusiran (Image Source: Reference [3])

Abstracts from the ASH annual meeting showed that, in a randomized, open-label Phase 3 clinical trial, fitusiran met the primary and secondary endpoints. Compared with on-demand bypassing agent treatment, it significantly reduced the annual bleeding rate (ABR) for spontaneous bleeds, joint bleeds, and total bleeds requiring treatment. In the fitusiran group, 65.8% of patients had an ABR of 0. Moreover, prophylactic fitusiran treatment demonstrated efficacy in both hemophilia A and B patients with inhibitors. Specific data are shown in the figure below.

▲Phase 3 Clinical Trial Results of Fitusiran (Image Source: Reference [2])

References:

[1] New data in blood cancers, hemophilia, and other hematological disorders to be presented at ASH 2021. Retrieved November 7, 2021, from https://www.sanofi.com/en/media-room/press-releases/2021/2021-11-04-16-30-00-2327804

[2] 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). Retrieved November 7, 2021, from https://ash.confex.com/ash/2021/webprogram/Paper150273.html

[3] Development of a Pharmacokinetic-Pharmacodynamic (PK-PD) Model of Fitusiran, an Investigational RNAi Therapeutic Targeting Antithrombin for the Treatment of Hemophilia in Patients With and Without Inhibitors. Retrieved June 19, 2020, from https://www.alnylam.com/wp-content/uploads/2017/07/Attarwala_Fitusiran-PKPD_ISTH-2017_09July2017.pdf

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