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

Rehan M. Hussain, Ashley E. Neiweem, Viral Kansara, Alon Harris, Thomas A. Ciulla

Research output: Contribution to journalReview article

5 Scopus citations

Abstract

Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of 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 opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.

Original languageEnglish (US)
Pages (from-to)861-869
Number of pages9
JournalExpert Opinion on Investigational Drugs
Volume28
Issue number10
DOIs
StatePublished - Oct 3 2019

Keywords

  • AKB-9778
  • ARP-1536
  • AXT107
  • Age-related macular degeneration
  • Tie-2 receptor
  • angiopoietin
  • diabetic macular edema
  • faricimab
  • nesvacumab
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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