Diabetic nephropathy is a serious and progressive complication of diabetes that leads to chronic loss of kidney function.
Diabetic Nephropathy and the Role of Nitric Oxide Deficiency:
Diabetic Nephropathy, or diabetic kidney disease, is a common, serious microvascular complication of type 2 diabetes that leads to chronic loss of kidney function over time. As it progresses, it often leads to end stage renal disease (ESRD) which requires chronic dialysis treatment or kidney transplant.
Diabetic Nephropathy is characterized by elevated levels of albumin and other proteins in the urine. This is a sign of kidney dysfunction, as protein does not pass into the urine if the kidneys are healthy.
We believe nitric oxide deficiency plays an important role in the chain of events leading to Diabetic Nephropathy. In the healthy kidney, nitric oxide signaling promotes the relaxation of vascular smooth muscle cells, blocks endothelial cell activation, and inhibits excessive vascular proliferation, inflammation and fibrosis. In patients with diabetes, however, nitric oxide signaling is frequently impaired, which may lead to decreased blood flow, inflammation and fibrosis in the kidneys and Diabetic Nephropathy.
The association between deficient nitric oxide Diabetic Nephropathy has also been established genetically; those who are genetically predisposed to be deficient in a key nitric oxide-producing enzyme in the vasculature are more likely to develop Diabetic Nephropathy.
Praliciguat is an investigational, oral sGC stimulator that in preclinical studies distributes extensively into tissues, including to both kidney and adipose tissue. We believe this makes it well suited to treat Diabetic Nephropathy. By amplifying nitric oxide signaling, we believe praliciguat may compensate for deficits in this signaling pathway and ameliorate the symptoms and progression of Diabetic Nephropathy. In this way, we believe praliciguat has the potential to improve kidney function, appropriately regulate blood flow in the kidneys, and reduce or prevent kidney inflammation and fibrosis. Based on data from a Phase 2a study in patients with type 2 diabetes and hypertension, we believe praliciguat may also have positive metabolic effects, including improving insulin sensitivity and decreasing LDL cholesterol and triglyceride levels in patients with cardiometabolic disease.
Praliciguat is currently in a dose-ranging Phase 2 study in adult patients with DN that is expected to enroll approximately 150 patients. We expect results from this study in the second half of 2019.
Facts & Figures:
- The World Health Organization estimates that there are over 400 million adults with diabetes globally.
- Up to 40% of all patients with diabetes have Diabetic Nephropathy.
The economic burden of caring for Diabetic Nephropathy patients is high due to the cost of treating end stage renal disease as well as the strong association of Diabetic Nephropathy with cardiovascular disease.