Replies to post #7087 on GTC Biotherapeutics (fka GTCB)

[DewDiligence]

>on the severe v. moderate sepsis point that Dew raised, I see that the Leo study does specify predicted mortality of 30-60%, but it also characterizes this as a study of "severe" sepsis.<

Some investigators (including those in the Kybersept study) use the terms moderate risk, high risk, and very high risk to denote the categories I’ve called low risk, moderate risk, and high risk, respectively. However, the categories themselves are the same regardless of what they are called: the three categories correspond to a predicted probability of death of <30%, 30-60%, and >60%, respectively.

That the description of Leo’s phase-2 trial says the indication is “severe sepsis” means nothing in itself; the entry requirement of 30-60% predicted probability of death means the patients are in the category I call moderate risk.

>in the published study [#msg-26125791], the survival is 11/16 and 12/17 in the two arms, 31 and 35% [mortality], which is at the low end of the predicted mortality in the Leo study.<

The study you cited had the same eligibility requirements as the Kybersept study, and the predicted probably of death was not used as an entry requirement. The 31% and 35% figures are thus averages over the three risk categories. Given the fact that this trial was tiny (33 patients) and included patients from all three risk groups, it’s hardly surprising that no significant difference in mortality between the arms was found. Regards, Dew

[DewDiligence]

>as to the short duration, the protocol in the published study is 4 days of infusion and the Leo study is 5 days -- is one extra day likely to be that important?<

Probably not. What is more consequential than the number of days of treatment is whether a trial’s protocol allows for antithrombin dose adjustment based on a patient’s antithrombin level during treatment. Leo’s trial presumably permits such adjustment.

[vinmantoo]

Mouton,

I should have read your post before making my last post as I was wrong about some comments. You are right that LEO will be infusing for only 5 days as opposed to 4 days in the study, which surprises me that they wouldn't be monitoring and redosing later in an effort to maintain ATIII at more physiological levels. Second, there is no mention of prescreening for ATIII levels prior to administration. However, the paper in question tried to use extremely high doses of ATIII so it is unlikely that LEO will do the same. Still, I think these are points which should be clarified by someone calling IR of GTCB.


Nice work,

Vinnys