Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration

ABSTRACT

Introduction: Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies.

Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF – but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability). X-82 is an oral anti-VEGF and anti-PDGF being tested in phase 2 studies. Topical anti-VEGF ± anti-PDGF drugs under study include pazopanib, PAN-90806, squalamine lactate, regorafinib, and LHA510. Sustained-release anti-VEGF delivery treatments, such as the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305 aim to reduce the burden of frequent injections. Gene therapies with new viral vectors hold the potential to induce sustained expression of anti-angiogenic proteins via the retina’s cellular apparatus, and include AVA-101/201, ADVM-202/302, AAV2-sFLT01, RGX314, and Retinostat.

Expert opinion: There are many emerging anti-VEGF treatments that aim to improve visual outcomes and reduce the treatment burden of nAMD.

KEYWORDS:

• Abicipar pegol
• brolucizumab
• neovascular age-related macular degeneration
• gene therapy
• nesvacumab
• platelet-derived growth factor
• pegpleranib
• Tie-2 receptor
• vascular endothelial growth factor
• X-82

Declaration of interest

TA Ciulla has had an employment relationship with Ophthotech Corporation; however, this manuscript was written during his work as a Volunteer Clinical Professor of Ophthalmology at Indiana University School of Medicine, and none of the work herein represents any official position or opinion of Ophthotech Corporation or its management. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper was not funded