Shire has kicked off two mid-stage trials assessing Vascugel - which is being developed by Shire under the name SRM003 - for enhancing blood vessel repair in patients with end-stage renal disease (ESRD) receiving haemodialysis.
Before patients can undergo haemodialysis, an arteriovenous (AV) access site must be created where blood can be removed, filtered and returned to the body.
In most cases, AV access is achieved through either an AV fistula (AVF), where the vein is connected directly to the artery, or an AV graft, where the vein and artery are connected via a synthetic tube.
Shire notes that there are around 100,000 AV fistulas and 60,000 AV grafts occurring annually in the US. But complications - such as infection, blood clots, and narrowing of the vessel - are common and frequently lead to access failure.
In fact, an estimated 60% of AV grafts fail after one year, requiring an additional procedure to restore flow or to create another access site, Shire said.
Moreover, “there are currently no approved therapies that directly target the underlying physiological processes associated with the failure of AV access sites in haemodialysis patients,” said Steven Steinberg, MD FACP, president of the California Institute of Renal Research and the coordinating investigator for both studies, highlighting the current unmet medical need.
When placed outside the blood vessel, it is hoped that the SRM003 gelatin matrix containing endothelial cells will provide a continuous supply of multiple growth regulatory compounds to the underlying cells within the blood vessel while being protected from the effects of blood flow in the vessel(s) or complications resulting from being in direct contact with the point of injury.
Two Phase II trials
As such, the first Phase II study, AVF01-SRM003, will evaluate the efficacy and safety of SRM003 in improving the rate of AVF maturation and use in subjects with ESRD having surgery to create of a haemodialysis access site in the upper extremity.
The second study, AVG01-SRM003, will look at the efficacy and safety of SRM003 in extending the duration of primary patency - i.e. how long the access site remains 'open' - after placement of an AVG in such patients.
Both are multicentre, single-blind, randomised, controlled studies, that aim to enroll around 200 adult subjects.
Shire obtained the rights to Vascugel through it purchase of Pervasis Therapeutics in April last year. The product has received Orphan Product and Fast Track designation from the US Food and Drug Administration and Orphan Product designation from the European Medicines Agency.