The French biotech Genkyotex has announced Phase II results for GKT137831 in diabetic kidney disease. The NOX1-4 inhibitor failed to reduce albuminuria.
Genkyotex focuses on developing inhibitors of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) enzymes which are expressed by the NOX-gene family (NOX 1-5). NOX enzymes generate reactive oxidative species (ROS) which if overproduced, can cause various interruptions or overstimulation of cell-signalling pathways, resulting in tissue damage (such as kidney nephrons).
Diabetic Nephropathy (DN) is a progressive renal disease caused by damage to the capillaries in the nephric glomeruli. This increases the permeability of the glomerulus and therefore leads to loss of proteins such as albumin from the blood which are then excreted (albuminuria). DN is the key precursor to more severe conditions such as end-stage renal disease (ERSD), which in turn has its own complications, requiring hemodialysis and where possible, kidney transplantation.
Development of the GKT137831 candidate (a NOX1 & NOX4 inhibitor) showed considerable promise in its phase I trial tested on up to 100 patients with DN and no adverse effects.