Emerging clinical data suggests that targeting the anticoagulant protein, antithrombin (AT), could be a promising approach to prevent bleeding in patients with hemophilia. This question has been the focus of work of Dr. John Pasi of Queen Mary University of London.

Fitusiran is a once-monthly, subcutaneously (SC) administered, investigational RNA interference therapeutic that targets endogenous AT with the aim to improve thrombin generation (TG) and rebalance hemostasis in patients with hemophilia A or B with or without inhibitors. Fitusiran has recently garnered promise based on findings from the Phase 1 study results and the follow-on Phase 2 open-label extension interim analysis, which demonstrated that it was well tolerated and led to dose-dependent AT lowering, increased TG, and decreased frequency of bleeding.

The latest presentation of the Phase 2 open-label extension study reported the interim safety and efficacy results of fitusiran prophylaxis for patients with hemophilia A or B with or without inhibitors from the most recent data cut in May 2019. Patients on study had received monthly fixed doses of fitusiran 50 mg or 80 mg SC.

This dataset evaluated 34 enrolled patients (hemophilia A, n=27; hemophilia B, n=7), who have now been followed for up to 3 years, with a median exposure of approximately 23 months. Of the 33 patients examined, the once-monthly fitusiran prophylaxis SC dose achieved sustained AT lowering, which led to TG levels approaching the lower end of the range seen in healthy volunteers. Exploratory analysis showed an overall median annualized bleeding rate (ABR) of 1.08, without the development of antibodies against fitusiran. Replacement factors or bypassing agents were only used during breakthrough bleeds, in accordance with a with a revised treatment guideline.

Dr. Pasi and his team’s findings indicate that fitusiran prophylaxis was well tolerated and resulted in a sustained AT lowering effect in the context of hemophilia. Moreover, this effect was associated with a low ABR for up to 3 years These findings support fitusiran as a promising investigational approach for rebalancing hemostasis in the setting of hemophilia A or B, with or without inhibitors with additional benefits of low-volume SC administration and monthly dosing.

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