Dr. Cox mentioned on the third quarter call that there is a paper that shows why LEO and GTCB have significant reason to believe that AT can be approved for DIC in patients that have Sepsis. This message responds to Dew’s post which contains the paper.
This is a request for those on this board who are interested or experienced in clinical data to provide feedback!
Why is this paper important? It indicates, with a very high likelihood and significant sample size that in the first 90 days, AT can save the lives of 85% of DIC patients who would have died on Placebo alone. This AT indication is entering Phase II and there are hundreds of thousands of patients in both Europe and US that would take AT each year if it works out. It appears that 40% of those who have Sepsis develop DIC.
With Placebo only, DIC increases your 90-day mortality from 32.9% with sepsis alone to 50.4% with both sepsis and DIC (that is a 53% higher chance of dying). This is based on 275 patients.
With AT vs. Placebo, DIC increases your 90-day mortality from 32.9% with sepsis alone to 34.4% with both sepsis and DIC (that is a 4.5% higher chance of dying or an 85% higher survival rate than Placebo). This is based on 263 patients.
Background:
All (no cherry picking) of the 563 patients from the Kybersept trial who did not receive heparin and that had DIC testing (known to have or not have DIC) were utilized. A low number (18 out of 563) of patients dropped out during the final 2 months of the study, but all 563 were available at 28 day mortality determination. Results below show number of participants and the drop from 28 day to 90 day. The 18 that dropped were spread over three out of four groups as shown below.
An improved and standardized panel of tests, which is becoming better accepted was used to determine DIC.
Mortality was the main end-point.
Approximately half of the above patients did not have DIC which was useful for showing survival rate for Sepsis without DIC as a baseline.
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Results:
AT reduced the mortality rate for patients with DIC & Sepsis to nearly the mortality rate of patients with just Sepsis alone. P values for AT vs. placebo for DIC patents were 0.024 @ 28 days and 0.015 @ 90 days. P values were not adjusted for multiplicity of tests but the raw numbers and setup seems very strong.
28 days (% died):
With Sepsis Alone:
Placebo: 22.2% (n=162)
AT: 22.1% (n=172)
With DIC & Sepsis:
Placebo: 40.0% (n=115)
AT: 25.4% (n=114)
AT% died with DIC reduced to nearly as low as the 28-day Placebo level for people without DIC!
90 Days (% Died)
With Sepsis Alone:
Placebo: 32.9% (n=155) Only 7 dropped out during study
AT: 29.9% (n=167) Only 5 dropped out during study
With DIC & Sepsis:
Placebo: 50.4% (n=115) Zero dropped out during study
AT: 34.4% (n=108) Only 6 dropped out during study
AT% died reduced to nearly the 90 day Placebo level for people without DIC!
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There was one complication mentioned but it is considered insignificant statistically:
Major Bleeding complication at 28 days was 7.0% in patients with DIC who took AT vs. 5.2% for patients with DIC who took placebo. The difference was considered statistically insignificant (P=0.6).
Dew,
Here are some potential questions to put to a vote on the board (as we discussed earlier):
1: What do you think is the closest probability of eventual approval of AT for DIC in Sepsis based on review of the clinical paper “Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation”.
A) 80%, B) 60%, C) 40%, D) 20%, E) 5%
2: What do you believe is the weakest aspect of the above paper:
a. Sample size
b. Retrospective nature
c. P values were not adjusted for multiplicity of tests.
d. Other: _____________ (please share)
3: What do you think will/would have the largest positive impact on GTCB’s success.
A) Approval of AT for DIC in Sepsis
B) Approval of AT by US FDA
C) Multiple manufacturing agreements
D) The LFB collaboration agreement
E) The LEO collaboration agreement
F) Limit share dilution
G) Other:_______________ (please share)
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