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

ABSTRACT

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

KEYWORDS:

• Ang/Tie
• angiopoietin/Tie pathway
• anti-VEGF
• retina diseases
• macular degeneration
• diabetic macular edema

Article highlights

• The Angiopoietin/Tie (Ang/Tie) pathway is involved in vascular development and growth under physiological and pathologic conditions, including wet age-related macular degeneration (w-AMD), diabetic macular edema (DME), and retinal vein occlusions (RVOs).

• In preclinical and clinical studies, the dual inhibition of the Ang/Tie pathway and VEGF-A has conferred better outcomes than anti-VEGF monotherapy.

• Several novel drugs targeting the Angiopoietin/Tie pathway are being investigated; these include ARP- 1536, REGN910-3, AXT107, AKB-9778, and faricimab.

• Faricimab is a bispecific antibody, which simultaneously binds to VEGF-A and Ang-2. Preliminary results from phase III trials LUCERNE and TENAYA for patients with w-AMD and RHINE and YOSEMITE for patients with DME have shown promising results with a longer treatment interval (16 weeks).

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has received honorarium for consultancy and lecture fees from Allergan, Bayer, Boehringer Ingelheim, Novartis, and Roche. One reviewer is a co-author on patents related to targeting of the angiopoietin pathway in eye disease and his/her laboratory has also received research funding from Bayer. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.