Abstract
Purpose :
Neovascular age-related macular degeneration (nAMD) represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF agents. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. LX102 is developed by recombining the AAV2 capsid and the gene coding for VEGF trap. The purpose of this study was to assess the safety, tolerability and preliminary efficacy of a single subretinal injection of LX102 in patients with nAMD.
Methods :
In this open-label, single-center trial, we enrolled subjects with nAMD at Shanghai General Hospital. 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 ETDRS letters. And the study eye must have received at least 2 anti-VEGF treatments within 6 months prior to screening. After the enrollment, all subjects received an intravitreal injection of aflibercept (2mg/0.05mL), followed by subretinal injection of LX102 (2×1010 vg) two weeks later. The study eyes were 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 medicalresearch.org (medical research registration system of China), number MR-31-22-004106.
Results :
From Jun 14, 2022, to Nov 29, 2022, we enrolled five subjects (all men; mean age of 72.8±5.1 years old) who received the prespecified treatment regimen. Subretinal injection of LX102 was overall well tolerable. No LX102-related adverse events were noted; procedure-related adverse events (conjunctival hyperemia, post-operative visual acuity reduction and mild cell debris in the anterior vitreous) were generally mild and self-resolving. Clinical laboratory assessments generally remained unchanged from baseline. All subjects were free of anti-VEGF Rescue Injection till the latest visit. Compared to baseline, the mean BCVA of the study eyes increased by 2.2 ETDRS letters, and the mean central subfield thickness (CST) decreased by 246.8 μm.
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 anti-VEGF treatments and maintain long-term visual outcomes.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.