GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Re: Miscellaneous DIC questions

>Does anyone know [whether] in DIC are all factors equally consumed or is AT consumed more than others?<

In DIC, the clotting mechanism itself gets thrown out of whack. For clotting to occur (either normally or in DIC), a complex cascade of chemical reactions with feedback loops is triggered (#msg-16968590, #msg-16968800).

>Why does antithrombin seem to be more important than other factors?<

AT is not itself a “factor” but it inhibits the formation of various clotting factors, especially thrombin (a.k.a. FIIa). AT’s activity against multiple clotting factors makes it an especially powerful place to intervene in the clotting cascade.

>Has anyone ever done any studies where various factors were given in various combinations?<

To treat DIC, you want to give something to inhibit clotting, so you wouldn’t use a clotting factor per se. Within the natural clotting cascade, there are choices other than antithrombin to accomplish the desired inhibition. Artisan Pharma is investigating the use of thrombomodulin (#msg-14524596). Xigris from LLY, the only approved drug for sepsis, is a recombinant form of Activated Protein C.

>Do you think an arm with ATryn + Xigris would prove anything beneficial? I know Xigris is a failure and I am quite surprised it ever was approved, but considering Xigris and ATryn would have different MOA, is there any potential when combined you could get stellar results?<

This is something to think about way down the road, IMO. Xigris has a very narrow therapeutic window; trying to incorporate it into a pivotal DIC trial for Atryn would greatly increase the risk of failure. Regards, Dew