Technology
Elastin and collagen fibers are the major extracellular components of the blood vessel wall. Collagen fibers provide strength to the vessel while elastin fibers determine vessel diameter, provide elasticity and regulate cellular proliferation and migration. Proteon has developed a method of degrading elastin fibers in treated segments, while leaving the collagen fibers intact and preserving structural integrity.
Non-clinical studies by Proteon suggest that elastin degradation may result in vessel dilation and reduced neointimal hyperplasia in the vessel lumen. An increase in cross sectional lumen area would reduce the impact of vessel stenosis, potentially prolonging vessel patency (function). PRT-201 treatment is administered as a single dose that can be applied topically to the external surface of exposed vessels during surgery or injected into the wall of blood vessels using drug delivery catheters during an endovascular procedure. Thus, the drug could potentially be used in a variety of surgical and endovascular procedures to improve the patency of treated vessels.
Clinical Development Programs
Proteon Therapeutics is currently pursuing clinical development programs for PRT-201 in two hemodialysis vascular access indications: arteriovenous fistulas and arteriovenous grafts.
Vascular Access for Hemodialysis
Most patients whose kidneys no longer function adequately undergo chronic hemodialysis, a blood purification process in which blood is passed through a dialysis machine that removes substances normally excreted by the kidney. Hemodialysis requires surgical creation of a vascular access so blood can be efficiently drawn through the dialysis machine. There are two main types of permanent vascular access sites: arteriovenous fistulas (AVFs), where a vein is surgically connected to an artery, and arteriovenous grafts (AVGs), where a vein is connected to an artery via a segment of artificial tubing.
Once functional for hemodialysis, AVFs and AVGs are at risk of losing patency over the subsequent months and years. Patency loss manifests as thrombosis (blood clotting) or diminished blood flow, resulting in inadequate dialysis and increased morbidity and mortality. Currently available treatments to restore blood flow fail to provide a durable benefit, and patients may thus endure repeated interventions and surgical procedures associated with complications, poor outcomes and higher cost of care.
Proteon believes there is potential for using PRT-201 as a therapy to improve the outcomes associated with surgical creation of AVFs and AVGs. Proteon commenced enrollment in its AVF Phase 1/2 clinical trial in late 2008, and in its AVG Phase 1/2 clinical trial in 2009. Proteon is currently identifying clinical sites to participate in upcoming Phase 2 AVF and AVG clinical trials expected to commence in 2011.
Other Potential Indications
The Company believes that PRT-201 may be useful to treat other vascular diseases in which reduced blood flow impairs clinical function, including peripheral arterial disease (PAD) and coronary artery disease (CAD).
