Replies to post #7078 on GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Re: Moderate vs severe sepsis

Thanks for your post. The takeaway message here is that antithrombin works best in DIC/sepsis patients with moderate disease; in severe sepsis, patients are generally too ill for any treatment to be effective.

In Leo’s phase-2 trial, eligibility is restricted to patients whose predicted mortality—based on an industry-standard model—is between 30% and 60% (i.e. predicted survival of 40-70%): #msg-21636676. This is a very important feature of the trial that has often been overlooked. Regards, Dew

[vinmantoo]

I just scanned the article. This section from the discussion explains some of the limitations inherent in this study, including a short duration of ATIII treatment and analysis of treatment effects, unscreened population with regard to ATIII levels etc. All in all, it isn't really anything relevant to rATIII usages in the sepsis trials.

<<the treatment with AT for four days did not reduce the overall 28-day mortality rates compared with placebo in a large phase III study [11]. Besides other factors [12], an insufficient dosage and duration of AT therapy could have been responsible for the negative results. In a recent study, prolonged duration of AT therapy guided by the actual activity, instead of a predefined dose, resulted in an effective modulation of coagulatory activation [13]. The effects of AT were thereby not evident until one week of therapy. Additionally, the selection of septic patients who may profit from AT therapy seems to be important. Patients with AT activity below 70% or patients undergoing continuous renal replacement therapies may profit most [20]. Our data seem to confirm these findings, as we did not find alterations of coagulation parameters during the four day treatment with high doses of AT in a population of septic patients not selected by AT activity or a need for renal replacement therapy.>>