Emerging solutions for neovascular age-related macular degeneration

To summarize emerging therapeutic strategies for neovascular (wet) age-related macular degeneration (nAMD), with emphasis on recent translational and clinical developments.

The nAMD treatment landscape is rapidly evolving. Gene therapies (e.g. ABBV-RGX-314, ADVM-022, and 4D-150) have demonstrated sustained intraocular anti-VEGF expression with reduced injection burden in phase 2 and 3 programs, validating the 'biofactory' concept. Tyrosine kinase inhibitors delivered via intravitreal or suprachoroidal implants (e.g. EYP-1901, OTX-TKI, and CLS-AX) show potential for twice-yearly or less frequent dosing. Moreover, emerging therapeutic approaches increasingly target non-VEGF pathogenic pathways, reflecting a shift toward mechanistically diverse vascular stabilization and neuroprotection strategies. These include multitargeted biologics that couple anti-angiogenic and anti-inflammatory effects (e.g. KSI-501, IBI-302, and AG-73305), as well as agents modulating FGF2 signaling, Wnt activation, complement regulation, and cellular metabolism.

Therapeutic innovation in nAMD is transitioning from incremental refinements in intravitreal anti-VEGF delivery to strategies aimed at extending durability or targeting alternative contributory pathways. Long-term safety, efficacy, and durability will determine which of these candidates redefine standard care.