LX102(Innostellar)

To assess the safety, tolerability, and preliminary efficacy of a single intravitreal injection of LX102-C01 in eyes with neovascular age-related macular degeneration (nAMD) followed up to 52 weeks.

Open-label, single-center, dose-escalation investigator-initiated trial (NCT05831007) with 2 cohorts (3E10 vector genome [vg] and 1E11 vg per eye).

Eyes with choroidal neovascularization secondary to nAMD, subretinal or intraretinal fluid, and a history of >2 anti-VEGF treatments in the past 6 months with a good response.

All patients received 1 injection of aflibercept 2 weeks before LX102-C01. Dose escalation started with 3E10 vg and increased to 1E11 vg per eye. Visual acuity, anatomy, and adverse events (AEs) were assessed. Macular choroidal thickness (CT) and vascularity were measured using a 6 × 6 mm scan on swept-source OCT angiography imaging.

The primary endpoint was AEs at 1 year. The secondary endpoints were best-corrected visual acuity (BCVA), central subfield thickness (CST), and incidence of rescue treatment. Exploratory endpoints included the macular hypoautofluorescent area, CT, and choroidal vascularity index (CVI).

Six eyes of 6 patients were included. There were no LX102-C01-related nonocular AEs. All LX102-C01-related ocular AEs were mild, predominantly anterior inflammation. There was no evidence of vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis. Two eyes from 2 patients developed recurrent subretinal fluid or hemorrhages that did not meet rescue criteria and resolved spontaneously after 1 to 2 months. All patients were free of rescue anti-VEGF treatments till the latest visit. Compared to baseline, BCVA maintained and CST decreased up to 12 months in both cohorts. The area of hypo-autofluorescence remained stable in both groups. The mean choroidal thickness (MCT) decreased from 162.1 μm to 147.1 μm (P = 0.03), but the CVI measurement showed no significant change (P = 0.6) up to 12 months. Changes in the MCT and CVI showed no statistically significant differences compared with the control group receiving standard aflibercept treatment.

LX102-C01 showed a favorable safety profile and potential efficacy in this preliminary 52-week study, with no observed macular atrophy, suggesting short-term tolerability of gene therapy associated anti-VEGF expression.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.