GTC Biotherapeutics (fka GTCB)

[DewDiligence]

Novo-Nordisk is working on its own enhancement
to NovoSeven (which goes off-patent in a few
years). The drug, called NN1731, is an analogue of
FVIIa that is made recombinantly. Clearly, this is a
program worth watching for GTCB investors.

The following abstract reports on an in vitro
comparison of NN1731 vs NovoSeven. NN1731
has not yet entered clinical trials.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Select+from+History&query_key=1&WebEnv=06H...

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Factor VIIa Analogue Normalises Clot
Formation in Whole Blood from Patients
With Severe Hemophilia A

Br J Haematol. 2007 Apr;137(2):158-65.

Sorensen B, Persson E, Ingerslev J.

Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Skejby, Aarhus N, Denmark.

This study evaluated and compared the haemostatic potential of a recombinant factor VIIa (rFVIIa) analogue (V158D/E296V/M298Q-FVIIa, NN1731, Novo Nordisk, Denmark) with rFVIIa (NovoSeven®, Novo Nordisk). In vitro studies were performed using freshly drawn whole blood (WB) from 14 patients with severe haemophilia A and two patients with inhibitory antibodies to FVIII, comparing NN1731 and rFVIIa against a buffer control. Fourteen healthy males served as controls.

Dynamic WB coagulation profiles were recorded, quantitatively illustrating the initiation [clotting time = CT (s)], propagation [maximum velocity = MaxVel (mm*100/s)] and termination [maximum clot firmness = MCF (mm*100)] as determined by thromboelastography with minute amounts of tissue factor (TF, Innovin((R))- final dilution 1:50 000, c. 0.12 pM) serving as activator. WB clot stability was assessed using a separate set-up including TF plus tissue plasminogen activator (final concentration 2 nmol/l), evaluating the MCF as well as the area under the elasticity curve (AUEC) after 60 min (mm*100*s).

NN1731 shortened the CT more markedly than rFVIIa. At the dose tested, NN1731 even shortened CT in haemophilia below the value of healthy males. [I’m not sure this is a good thing!] NN1731 accelerated MaxVel giving a value indistinguishable from that in healthy males. Furthermore, NN1731 increased clot stability more markedly than rFVIIa. Altogether, these in vitro studies on WB revealed a favourable haemostatic potential of NN1731 compared with rFVIIa in severe haemophilia A, both in the absence and presence of enhanced fibrinolytic activity.
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