Researchers predict an increase in vascular diseases due to the aging of the population and the increasing prevalence of risk factors such as hypertension and diabetes. To meet this medical need, treatments and techniques that can keep blood vessels open will be essential. Research into vascular remodeling offers hope for improved treatments and a better prognosis for people with a range of vascular problems including hemodialysis vascular access site failure and peripheral arterial disease.
Technology
Vascular remodeling is at the core of Proteon Therapeutics’ proprietary vasodilation drug development program. This technology focuses on elastases that modify the extracellular matrix of blood vessels, leading to immediate and persistent vessel enlargement and increases in blood flow. Local, permanent vasodilation could improve the medical outcome of common vascular surgeries, and may reduce treatment costs. Proteon Therapeutics’ first drug candidate, PRT-201 is currently in two phase 1/2 human clincial studies in hemodialysis vascular access. In preclinical studies conducted to date, PRT-201 led to vessel dilation that was:
Substantial - Arteries dilated by approximately 30-50% and veins dilated up to 75% depending upon the pressure within the vessel at the time of treatment.
Rapid - Dilation was complete after as little as 5 minutes of treatment.
Localized - Dilation was confined to the treated vessel segment with no systemic effect.
Persistent - Extracellular matrix was modified, leading to persistent relief of vasospasm and lasting dilation, both unique characteristics.
Safe - Vessels treated with PRT-201 did not rupture or form aneurysms.
Predictable - Removal of elastin with an elastase correlated with dilation.
As shown in the illustrations below, PRT-201 can be applied topically to the external surface of exposed vessels during surgery, or injected through angioplasty catheters.
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
Proteon’s first-in-man clinical studies are in hemodialysis vascular access - a large and growing market with significant unmet medical needs. Patients with kidney failure must undergo periodic external blood filtering with hemodialysis machines in order to remove fluid and metabolic byproducts from their blood. Vascular surgeons prepare patients for hemodialysis by creating high flow access sites in the body that can be connected to hemodialysis machines. These high flow access sites are created by connecting a medium-sized artery to a medium-sized vein, resulting in a “shunt” of blood through the vessels. There are two main types of chronic access sites: arteriovenous fistulas (AVFs), where the vein is surgically sewn directly to the artery, and arteriovenous grafts (AVGs), where the artery and vein are connected via a segment of artificial tubing. Unfortunately, these access sites are often difficult to create and prone to failure, resulting in treatment interruptions, hospitalizations, painful corrective surgical procedures, and premature death. Proteon believes there is potential for using PRT-201 as a therapy to facilitate the creation of dialysis access sites that are less susceptible to failure. 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.
Other Potential Indications
The Company believes that PRT-201 may be useful in other vascular indications, such as:
Pretreatment of small diameter veins to enable AVF and AVG placement in locations that would otherwise be ineligible for surgery;
Peripheral arterial disease (PAD); and
Coronary artery disease (CAD).
