Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab.

Abstract

This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

• Authors: Majid Khan, Aamir A Aziz, Noah A Shafi, Tayeb Abbas, Arshad M Khanani
• Journal: Cells (Cells) Vol. 9 Issue 8 (08 10 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32785136 (Publication Type: Journal Article, Review)

Chemical References

• ANGPT2 protein, human
• Angiopoietin-2
• Antibodies, Bispecific
• Antibodies, Neutralizing
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Receptor, TIE-2
• TEK protein, human

Topics

• Angiopoietin-2 (antagonists & inhibitors, immunology, metabolism)
• Antibodies, Bispecific (administration & dosage, immunology)
• Antibodies, Neutralizing (administration & dosage, immunology)
• Clinical Trials as Topic
• Diabetic Retinopathy (drug therapy)
• Humans
• Intravitreal Injections
• Molecular Targeted Therapy (methods)
• Receptor, TIE-2 (antagonists & inhibitors, metabolism)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (immunology)