Replies to post #6001 on GTC Biotherapeutics (fka GTCB)

[dewophile]

"Heparin is a polysaccaride (sugar based) and decreases the over efficiency of AT3 by effecting the glycolisation...The serendipitous recognition of this signifant subset [group receiving ATIII in the absence of heparin in kybersept] is a compelling arguement for the effectiveness of Atryn without Heparin for the treatment of DIC"

The data is fairly compelling that heparin antagonizes the antiinflammatory effects of ATIII (and DIC has an inflammatory component). However, the two seem to be additive when it comes to bleeding

for me the 3 most compelling reasons for thinking gtcb/leo will get positive data despite the failure of kybersept are the following, probably in this order:

1. avoiding excessive bleeding by avoiding concomitant heparin therapy (ATII had more bleeding compared w placebo, but most cases, particularly severe to catastrophic type bleeds like intracranial hemorrhages, occurred in patients cotreated with the two)
2. limiting inclusion criteria to those with intermediate prognosis (i.e. recongizing that those with less severe disease and limited organ dysfunction will survive regardless, and those with the most severe cases will die regardless of treatment stratification)
3. avoiding the antagonistic effect of heparin on ATIII's antiinflammatory activity

[keitern]

Pretty clear recap, thanks.

[waynebio]

Great thank you!

Looking at the paper, do you feel that AT3 may be nearly a cure for DIC since the probability of survival jumped up to the level of patents with just Sepsis in figure 1 on page 94. Do you think there may have been a reason why some patients were given Heparin and others were not...which may have had something to do with probability of survival? Would you agree that survival at 90 days is a high predictor of a cure based on the flat curve around 90 days on figure 1?

I guess my main concern is could the people that went into the AT3 without Heparin group had some difference that had a higher probability of survival. I suppose the criteria for determination of DIC was very well defined at this trial so it is unlikely to have been a problem.

I guess I just wonder, if this AT3 alone does not work for DIC, what are specific possible ways that this sub group study could have looked so good but been so wrong. It seems like with over 100 in each arm that the P values are able to have strong significance. What is an example of what might be different if AT3 alone was done for 100 patients? It seems unlikely that significance was a chance occurance in this subgroup alone. I suppose the only way we could fail is if there was some undisclosed reason or unsystematic method for segrigating patients into AT3 alone vs. AT3 with Heparin that may have put higher survival bias into the AT3 alone group. I know that this retrospective study is invalid for any serious determination because of after the fact creation of groups, I am just trying to unfold possible reasons that the data could possibily look good without actually being good. That way we can determine the likelhood of such problems.