Subretinal gene therapy AGTC-501 for X-linked retinitis pigmentosa in the Phase 1/2 Horizon study: Post-hoc analysis of microperimetry results in the high dose groups

Abstract

Purpose : X-linked retinitis pigmentosa (XLRP) is caused by mutations in the retinitis pigmentosa GTPase regulator gene, RPGR, leading to progressive nyctalopia, peripheral vision loss, and eventual central vision loss. Horizon is a Phase 1/2, open-label, dose-escalation study of patients with XLRP treated with subretinal AGTC-501. We undertook a post-hoc analysis of centrally-dosed patients in the high dose groups (Groups 4, 5, & 6) in Horizon who met the inclusion criteria for the Phase 2 Skyline study. Presented here are MAIA microperimetry data for this subset of Horizon patients.

Methods : Among patients treated in Horizon Groups 4, 5, & 6, there were 10 patients who met the criteria for this analysis: BCVA 35-75 letters, the presence of a detectable EZ line, and mean sensitivity on MAIA of 1-12 dB. Collective microperimetry results from these patients were compared from baseline to Month 12 and between treated and untreated eyes at Month 12.

Results : In the 29 males in Horizon receiving AGTC-501, there were no SUSARs or endophthalmitis reported, and no serious adverse events (SAEs) were deemed related to study agent. Adverse events (AEs) deemed related to study agent were all reported as non-serious and mostly Grade 1-2 in severity. While there was 1 Grade 3 AE of retinal depigmentation in the highest dose (Group 6), that eye was not eligible for this analysis.

Of the 29 patients in Horizon, 21 were dosed centrally, and 10 of these in Groups 4 (n=3), 5 (n=5), and 6 (n=2) met the criteria for the analysis. The mean age of these 10 patients was 23.8 ± 9.34 years.

In treated eyes, there was an improvement in mean MAIA sensitivity at 12 months. Untreated eyes had a decrease in mean sensitivity at Month 12. We also compared the difference in mean sensitivity in the treated and untreated eyes at month 12. Results are presented in Table 1.

Conclusions : A post-hoc analysis of data from patients in the highest dose groups in Horizon who would have been eligible for the Phase 2 Skyline study was undertaken. These patients demonstrated efficacy on microperimetry consistent with emerging data from Skyline and a favorable safety profile. Follow-up is ongoing through 5 years to assess long-term safety and durability of response.

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

 

Table 1. MAIA Mean Sensitivity Across the Whole Grid