Long-acting delivery and therapies for neovascular age-related macular degeneration

ABSTRACT

Introduction

Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease’s chronic nature and limited medication half-life.

Areas covered

This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained-release polymers and devices, reservoirs for intravitreal delivery, suprachoroidal delivery of small molecular suspensions and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed.

Expert opinion

The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high-dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes, demonstrating promise in expanding treatment durability.

KEYWORDS:

• Aflibercept
• age-related macular degeneration
• faricimab
• gene therapy
• port delivery system
• suprachoroidal delivery
• tyrosine kinase inhibitor
• vascular endothelial growth factor

Article highlights

• Recent FDA approvals of faricimab (Vabysmo) and high-dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike.

• Sustained delivery techniques to improve the safety, efficacy, and/or durability of targeted treatment for nAMD include reservoirs for intravitreal delivery (ranibizumab port delivery system), polymer-based intravitreal sustained-release devices (EYP-1901, OTX-TKI, KSI-301, KSI-501), suprachoroidal delivery of small-molecule suspensions (CLS-AX), and gene therapy biofactories (ABBV-RGX-314, ixoberogene soroparvovec, 4D-150).

• Alternative pharmacologic targets outside of focused anti-VEGF-A inhibition include therapies targeting inhibition of VEGF-C and D (OPT-302), the angiopoetin-2 (Ang-2)/Tie-2 pathway (faricimab), tyrosine kinases (OTX-TKI, EYP-1901, CLS-AX), and integrins (AXT107).

Declaration of interest

T Ciulla reports employment by, and holds equity in, Viridian Therapeutics, He holds equity in Clearside BioMedical and Nanoscope Therapeutics. In addition to Clearside and Nanoscope, he has served as a consultant for Ocuphire Pharma. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.