GTC Biotherapeutics (fka GTCB)

[DewDiligence]

ATryn vs Factor Xa Inhibitors

Factor Xa inhibitors in development such as apixaban and rivaroxaban (#msg-26900113) are not direct competitors of ATryn. Nor are low-molecular-weight heparins such as Lovenox, which act on FXa (#msg-24140012).

The diagram in #msg-26897966 depicts a simplified version of the clotting cascade. Thrombin (also called Factor II) catalyzes the conversion of FV->FVa and FVIII->FVIIIa; this creates a feedback loop though FXa that accelerates the production of more thrombin. (The feedback loop is omitted from the diagram in for simplicity.) Thus, inhibiting FXa inhibits the feedback loop and causes less thrombin to be produced. However, without a normal amount of circulating antithrombin, such inhibition is not effective, and an excessive—and clinically dangerous—amount of thrombin can be produced.

The above discussion applies to essentially any thrombotic condition. For disseminated intravascular coagulation (DIC), the need for a sufficient amount of circulating antithrombin is even stronger because AT’s anti-thrombin and anti-inflammatory properties are both vital in averting disease progression to organ damage and death.

Finally, it’s important to bear in mind that ATryn is intended to be a treatment for acute indications; its cost and administration by infusion make it impractical for chronic use.