Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease.

Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease. Expert Opin Investig Drugs. 2019 Sep 12;: Authors: Hussain RM, Neiweem AE, Kansara V, Harris A, Ciulla TA Abstract Introduction: The Tie-2/Angiopoietin pathway is therapeutic target in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage. Areas Covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally-administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously-administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert Opinio...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research