Wet AMD is the leading cause of blindness in the developed world in people aged over 50 years. It is caused by the abnormal growth and leakage of blood vessels at the back of the eye, which causes degeneration of the retina and vision loss.
These processes can be stimulated by members of the VEGF family of proteins, including VEGF-A, VEGF-C and VEGF-D.
Existing wet AMD therapies target VEGF-A. Opthea is developing OPT-302 which targets both VEGF-C and VEGF-D.
As an inhibitor of VEGF-C and VEGF-D, OPT-302 has the potential to block processes involved in wet AMD progression and improve vision.
Wet age-related macular degeneration, or wet AMD, typically affects individuals aged 50 years or older, and is the leading cause of blindness in the developed world. The disease is characterised by the loss of vision in the middle of the visual field caused by degeneration of the central portion of the retina (the macula). Abnormal growth of blood vessels in the choroid region of the back of the eye and into the overlying retina, as well as the leakage of fluid and protein from the vessels, causes retinal degeneration and leads to severe and rapid loss of vision if left untreated. Wet AMD affects central vision and the ability to see fine detail, such as that required to read, distinguish faces and drive a car.
The abnormal growth and leakiness of vessels is driven by increased production of signals that can induce blood vessels to grow and leak. The vascular endothelial growth factor (VEGF) family of proteins, which includes VEGF-A, VEGF-C and VEGF-D, is recognised as the most important signalling pathway driving these processes.
Current treatments for wet AMD target VEGF-A and represent a major advance in the management of the disease. However, approximately half of the people receiving the VEGF-A inhibitors Lucentis® or Eylea® only experience a stabilisation of their vision or a sub-optimal improvement in vision despite ongoing therapy. In a proportion of patients, vision continues to decline despite receiving anti-VEGF-A therapy.
There is great opportunity to improve patient responses by targeting more than one factor involved in disease progression.
Inhibition of VEGF-A, VEGF-C and VEGF-D can be achieved by combining OPT-302 therapy with an existing VEGF-A inhibitor, such as Lucentis® or Eylea®.
Opthea has reported encouraging results from a Phase 1/2A study in wet AMD patients. Data from this study indicated that OPT-302 is well tolerated when administered as a monotherapy and in combination with Lucentis® and suggested that combined administration of OPT-302 + Lucentis® may lead to improved clinical outcomes over Lucentis® alone (see Clinical Trials).