Replies to post #3055 on GTC Biotherapeutics (fka GTCB)

[jessellivermore]

This is indeed wonderful news.

[DewDiligence]

CJ Wiedermann has authored a new paper on
DIC/sepsis. As Wiedermann is the author of
another paper that GTC considers important
support for the DIC/sepsis program, this new
paper ought to be worth reading for anyone
here who is fluent in German.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...

>>
Endogenous Anticoagulant Therapy for Sepsis: Success and Failure

Internist (Berl). 2007 Mar 28;

[Article in German]

Wiedermann CJ.

Abteilung fur Innere Medizin, Zentralkrankenhaus und Akademisches Lehrkrankenhaus der Medizinischen Universitat Innsbruck in Bozen, L.-Bohler-Strasse 5, 39100, Bozen, Italien

Whereas antithrombin and tifacogin [the NVS drug that used to be owned by Chiron] failed to improve clinical outcome in cases of severe sepsis, drotrecogin alfa (activated) [Xigris] increased the chances of survival of patients with this condition. Concerns about efficacy and safety of drotrecogin alfa have been raised because of internal and external validity and internal consistency problems found in the PROWESS study, and because of the drug's single positive pivotal phase III documentation that led to restricted marketing authorisations for only a subgroup of studied patients whose randomisation had not been stratified. Concerns intensified with data from ADDRESS, the PROWESS follow-up, and pediatric studies.

It is difficult to make rational and safe recommendations for drotrecogin alfa use on the available evidence. Further trials have been suggested. The relevant bodies should review product approval in light of their own guidelines for marketing authorisations on the basis of single pivotal trials and request the further study required to prevent the possibility of patients receiving a non-efficacious and potentially lethal drug.
<<

[DewDiligence]

Scientific Rationale for Atryn in DIC/Sepsis

[Added preclinical study and second paper by Wiedermann.]


Primary support

“Treatment Effects of High-Dose
Antithrombin Without Concomitant
Heparin in Patients With Severe
Sepsis With/Without Disseminated
Intravascular Coagulation”
Kienast, J et al
J Thromb Haemost. 2006 Jan;4(1):90-7
Abstract: #msg-9313165.
Paper: http://ihub.bedida.net/Key_DIC_sepsis_article.pdf


Ancillary support

[See #msg-15250714 for
supplementary references.]

“Benefit/Risk Profile of High-Dose
Antithrombin in Patients with Severe
Sepsis Treated With and Without
Concomitant Heparin”
Hoffmann, J et al
Thromb Haemost. 2006 May;95(5):850-6.
Abstract: #msg-10993909.

“Antithrombin for Severe Sepsis?
Try Again But Without the Heparin!”
Jilma, B
Thromb Haemost. 2006 May;95(5):755.
(No abstract)

“High-Dose Antithrombin in the Treatment
of Severe Sepsis in Patients with a High
Risk of Death: Efficacy and Safety”
Wiedermann, CJ
Crit Care. 2006 Feb 34(2):285-92.

“Recombinant Human Antithrombin Inhibits
Thrombin Formation and Interleukin-6
Release in Human Endotoxemia”
Leitner, JM et al
Clin Pharmacol Ther. 2006 Jan;79(1):23-34.
Abstract: #msg-9313029.

“Endogenous Anticoagulant Therapy
for Sepsis: Success and Failure”
Wiedermann, CJ
Internist (Berl). 2007 Mar 28;
Abstract: #msg-18336592


Preclinical support

“Treatment Effects of Antithrombin on Coagulation
Abnormalities in Rats With Endotoxaemia”
Qiao, YJ et al
Abstract: #msg-18166129


The original KyberSept study

“High-Dose Antithrombin in Severe
Sepsis: A Randomized Controlled Trial”
Warren, B et al
JAMA 2001 286:1869
http://scalpel.stanford.edu/articles/AT3.pdf