Subretinal rAAV2-based VEGF-Trap gene therapy for neovascular age-related macular degeneration: Preclinical assessment and phase 1 trial results.

Li, Tong; Feng, Jingyang; Yang, Xiaolu; Yang, Shiqi; Chen, Jieqiong; Wu, Yidong; Li, Xiaosa; Ni, Zhuoyu et al. · Cell Rep Med · 2026

rct · Level II

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Abstract

Intraocular vascular endothelial growth factor (VEGF) antagonists for neovascular age-related macular degeneration (nAMD) require frequent injections, leading to treatment burden and suboptimal outcomes. LX102 is an rAAV2-based gene therapy encoding VEGF-Trap via subretinal delivery. In laser-induced choroidal neovascularization (CNV) mouse models, LX102 prevents lesion formation and progression in a dose-dependent manner. In non-human primates, a single LX102 injection reduces grade IV CNV lesions by over 85% and maintains transgene expression for 26 weeks without drug-related ocular abnormalities. In a phase 1 dose-escalation study, 12 participants with nAMD receive a single LX102 administration (2 × 10<sup>10</sup> to 1.25 × 10<sup>11</sup> vector genomes/eye). LX102 is well tolerated with no clinically significant inflammation. Eleven participants (91.7%) require no supplemental anti-VEGF injections through 1 year, with stable visual acuity and reduced central subfield thickness in most cases. These findings support LX102 as a potential sustained therapeutic approach for nAMD. This study was registered at chinadrugtrials.org.cn (CTR20230194) and ClinicalTrials.gov (NCT06198413).