Clinical condition
After vascular surgery, an overgrowth of muscle cells can occur in the wall of the otherwise healthy blood vessels. Known as intimal hyperplasia, this is a significant problem as it can cause a complete blockage (de novo stenosis) of the blood vessel which usually results in the need for further surgery to avoid serious complications.
Patients who have kidney failure require their blood to be filtered through a dialysis machine to prevent them from dying. The process is normally carried out at least twice a week and involves the insertion of two needles into the patient — one to extract their blood and one to return it once it has been filtered. However, normal blood vessels cannot tolerate large needles being inserted into them repeatedly. One way to overcome this is to surgically insert a plastic tube between a vein and an artery in the patient's arm ("access graft"). Needles can then be repeatedly inserted into the graft to connect the patient to the dialysis machine.
Up to 60 per cent. of haemodialysis access grafts block within one year of being inserted due to de novo stenosis, so that repeat surgery must be performed. Such repeat surgery also frequently fails, but more rapidly as less suitable sites are used, and can only be performed a limited number of times. Alternative and more difficult routes to achieve filtration are then required. In these circumstances, the life expectancy of patients can be short.
|
Mechanism of action
Trinam® is a combination of a vascular endothelial growth factor (VEGF-D) gene packaged in an adenoviral vector (Ad 5) and a bio-degradable local drug delivery device made from collagen and invented by Ark. At the end of access graft surgery, the delivery device is fitted around the outside of the patient's vein where it has been joined to the access graft. The adenoviral vector carrying the VEGF gene is then injected into a space between the device and the blood vessel. This unique administration of the gene to the outside of the blood vessel rather than into the blood supply localises delivery of the gene to the target tissue site (smooth muscle cells) and reduces the risk of unwanted systemic effects. Once the VEGF gene is transfected locally, muscle cells in the vessel wall produce the VEGF protein which triggers the release of beneficial nitric oxide and prostacyclin. Ark has made a novel discovery by showing that the VEGF protein working via these two agents has a protective effect in vivo, keeping blood vessel walls in a healthy state and regulating muscle cell growth to prevent blocking of the vessel.
Development status
Ark has received approval from the FDA to conduct a Phase IIb trial in haemodialysis access surgery via the Special Protocol Assessment (SPA) process. Patient enrolment has now started in the US. Trinam® has been awarded Fast Track Status by the FDA and has been granted Orphan Drug Status in both the US and Europe.
In vivo data
prevents thickening of arterial wall
|
| Control - without Trinam® |
 |
| Control - with Trinam® |
 |
|
