Anglo-German drug development company Trigen has reported encouraging Phase II results with its direct thrombin inhibitor TGN 255 in the prevention of blood clot formation among patients on dialysis.
All patients who require dialysis to support their kidney function require anticoagulant therapy to stop their blood clotting whilst it is filtered through the dialysis membrane. In most cases the widely-used anticoagulant heparin is used to prevent this but, in a minority (around 2%) of patients, heparin can cause a catastrophic immunological reaction called heparin-induced thrombocytopenia (HIT).
Trigen’s strategy is to retain commercialisation rights to its pipeline in niche applications, including TGN 255 in dialysis, and once proof-of-concept is achieved license out ‘blockbuster’ indications. The company is developing TGN 255 alongside an oral formulation, TGN 167, which would allow the same anticoagulant to be used both for acute use in hospital and then chronic use as an outpatient.
A total of 28 patients undergoing chronic haemodialysis were enrolled in the open-label trial, which studied various doses of the drug across a maximum of three dialysis sessions. All patients received TGN 255 and intra-patient results were compared to a baseline haemodialysis session on heparin.
The trial concluded that a continuous infusion of TGN 255 was well tolerated at all dose levels tested. Increased doses of TGN 255 were associated with decreased extracorporeal circuit clotting and, in all cases, clotting was not clinically significant and no session was either interrupted or prematurely terminated. A clear dose-response was seen on coagulation measures.
The results were presented at the European Renal Association and European Dialysis and Transplantation Association Congress in Glasgow, Scotland.