The emerging role of the Angiopoietin-Tie pathway as therapeutic target for treating retinal diseases

Introduction: Several approaches have been investigated for treating wet age-related macular degeneration (w-AMD), diabetic macular edema (DME) and retinal vein occlusions (RVOs). The first-line treatment for these exudative retinal diseases consists of anti-vascular endothelial growth factor (VEGF) agents; however, the high treatment burden and the percentage of 'non responder' patients have highlighted the need for other approaches. Increasing evidence has shown the role of angiopoietin/Tie (Ang/Tie) pathway in the pathogenesis of these exudative retinal diseases; therefore, novel drugs targeting this pathway are under evaluation in clinical trials. Areas covered: We analyzed the novel, emerging drugs (ARP- 1536, the coformulation of aflibercept and nesvacumab, AXT107 and AKB-9778) that target the Ang/Tie pathway. These drugs are still in early phase clinical trials, but encouraging outcomes have emerged. We also discuss the clinical efficacy of faricimab, a bispecific monoclonal antibody that inhibits VEGF-A and Ang-2. Expert opinion: The simultaneous targeting of the VEGF and Ang/Tie pathways may be more beneficial than monotherapy in patients with exudative retinal diseases. Among the investigational drugs targeting the Ang/Tie pathway, faricimab has shown promising results in phase II/III trials and in the near future may represent a viable treatment option for the management of exudative macular diseases.