Diabetic retinopathy (DR) is a complication of diabetes caused by damage to blood vessels in the retina. It is a progressive retinopathy, the severity of which ranges from mild non-proliferative diabetic retinopathy (NPDR) to more advanced proliferative diabetic retinopathy (PDR).
Data suggests that deactivation of Tie2 is a key driver of the loss of pericytes that surround the capillaries, initial breakdown of the capillary wall, and the loss of capillaries (known as vasoregression or capillary dropout) which leads to worsening hypoxia and tissue ischemia. These are all hallmarks of early diabetic retinopathy. As the level of oxygen deprivation increases, the body responds by producing vascular endothelial growth factor (VEGF). The combination of upregulated VEGF and deactivated Tie2 leads to the development of vascular leakage, diabetic macular edema (DME), and the growth of abnormal blood vessels, proliferative diabetic retinopathy (PDR). Both of these conditions contribute to the loss of visual function associated with diabetic eye disease. AKB-9778's ability to restore Tie2 activation coupled with the less invasive route of administration provides a unique opportunity to be used in earlier-stage diabetic eye disease and potentially prevent vision loss caused by progression to DME or PDR.
The patient population in early-stage DR is roughly five times the size of that in DME.
Current Treatment Options
Laser photocoagulation is sometimes used to treat DR prior to the development of DME or PDR. This treatment entails using a high-energy laser to destroy diseased retinal tissue and cauterize leaking blood vessels. While this therapy temporarily prevents further vision loss, it does not address the pathology of constant and prolonged vascular damage that happens in the diabetic retina, and is therefore not considered a disease-modifying therapy. In addition to destroying retinal tissue, laser photocoagulation can be associated with several adverse events including transient decreases in central vision, black spots in the center or around the center of a patient’s vision, delayed or impaired adaption of vision in dark settings, or proliferation of abnormal blood vessels leading to macular edema.
Lucentis® has recently received FDA approval for treatment of DR (Genentech Press Release, 17April2017) based on the results of the RISE/RIDE clinical trials as well as DRCR.net Protocol S in patients with PDR (Writing Committee for the Diabetic Retinopathy Clinical Research Network, 2015). Two trials are currently underway to test the efficacy of Eylea® in patients with moderately severe to severe DR without DME (the PANORAMA study - NCT02718326 sponsored by Regeneron; and Protocol W - NCT02634333 sponsored by DRCR.net). However, to date, there is no clinical trial data on the efficacy of anti-VEGF therapy in the treatment of NPDR in patients prior to the development of DME or PDR.