Subretinal LX102 gene therapy for neovascular age-related macular degeneration (nAMD): 9-month follow-up of a phase 1 clinical trial

Abstract

Purpose : The purpose of this study was to assess the safety, tolerability and preliminary efficacy of a single subretinal injection of LX102 gene therapy in patients with neovascular age related macular degeneration (nAMD) up to 52 weeks.

Methods : In this open-label, multi-center phase 1 clinical trial, we enrolled subjects with nAMD. Eligible subjects had to be over 50 years old, have active choroidal neovascularization (CNV) secondary to nAMD, with best corrected visual acuity (BCVA) of 5~63 letters measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. After the enrollment, all subjects received a single intravitreal injection of aflibercept (2mg/0.05mL), followed by subretinal injection of LX102 two weeks later. Subjects were assigned to receive either 2 × 10¹⁰ vector genomes (vg; low-dose cohort), 2 × 10¹⁰ vg (medium-dose cohort) or 1.25 × 10¹¹ vg (high-dose cohort) of LX102. During the follow-up period after LX102 administration, the study eye would be evaluated for the need of anti-VEGF Rescue Injection during the follow-up based on prespecified criteria including BCVA, optical coherence tomography (OCT), and fundus photography. This trial is registered on chinadrugtrials.org, number CTR20230194.

Results : We enrolled 9 subjects (mean age of 70.2 years, standard deviation [SD] 6.7) in this study who received the prespecified treatment regimen (3 subjects in the low-dose cohort, 3 subjects in the medium-dose cohort and 3 subjects in the high-dose cohort). Subretinal injection of LX102 was generally well tolerated. No LX102-related adverse events were noted; post-operative adverse events, i.e., conjunctival hyperemia (67% of subjects) and increased intraocular pressure (IOP) (11.1% of subjects) were generally mild and resolved within days to weeks. No evidence of vasculitis, retinitis, choroiditis, vascular occlusions or endophthalmitis was reported. Up to date, only one of the subjects required anti-VEGF Rescue Injection. Mean BCVA changes of low-dose cohort, medium-dose cohort and high-dose cohort were -0.7, 3.7 and 6 ETDRS letters, respectively.

Conclusions : Subretinal LX102 injection was well tolerated in nAMD subjects. And these results support LX102 gene therapy as a potential treatment option to reduce the burden of frequent anti-VEGF treatments and maintain the best long-term visual outcomes.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.