Addressing complications of diabetes

Compound summary

Evolva is developing EV-077 for the treatment of complications of diabetes. EV-077 is an oral, small molecule compound, belonging to a new structural class. Preclinical and early clinical studies indicate the compound has potential as an inhibitor of the effect of isoprostanes and prostanoids on the thromboxane prostanoid receptor. Multiple patent applications have been filed regarding the compositions and uses of EV-077. Evolva owns all rights to EV-077.

The treatment of complications of diabetes

The mechanism of action of EV-077 means that it can potentially ameliorate or prevent a range of diabetic complications (including loss of kidney function and increased risk of thrombosis) that derive from the following chain of events:

• Diabetic patients have a reduced sensitivity to insulin which increases overall glucose levels in the body

• The increase in glucose increases oxidative stress

• This oxidative stress generates a high level of isoprostanes and prostanoids

• The isoprostanes and prostanoids chronically activate thromboxane receptors, that are located on the vasculature walls and on the surface of platelets

• Activation of the thromboxane receptors increases vascular inflammation and platelet reactivity

• A high level of vascular events and a progressive deterioration of circulatory and renal function are observed.

Progress

In July 2011 Evolva announced the completion of a Phase I multiple ascending dose study with an extended-release oral formulation of EV-077 for the treatment of complications of diabetes.

In November 2011, Evolva announced receiving regulatory clearance to progress EV-077 into Phase IIa clinical studies for the treatment of complications of diabetes. It will be a single-centre study, conducted in Germany. The intention is to enrol up to 64 evaluable patients. The study will be randomised, double-blind, and placebo-controlled, and investigate the efficacy and safety of EV-077 in type II diabetics with a heightened risk of diabetic vascular complications. Measurements will include oxidative stress, vascular inflammation, blood flow and platelet reactivity, as well as markers of the function of organs that are often impaired in diabetes (e.g. kidney, retina).

In parallel to the Phase IIa study, Evolva is conducting epidemiological studies to identify patient sub-groups that expedite further clinical development and approval process.

Scientific paper

Effect of Pharmaceutical interventions targeting thromboxane receptors and thromboxane synthase in cardiovascular and renal diseases. Request download