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The following is a summary of “Subretinal Gene Therapy Drug AGTC-501 for XLRP Phase 1/2 Multicenter Study (HORIZON): 24-Month Safety and Efficacy Results,” published in the December 2024 issue of Ophthalmology by Yang et al.
Researchers conducted a retrospective study to examine the safety and efficacy of subretinal gene therapy using AGTC-501 (rAAV2tYF-GRK1-RPGR) in male participants with X-linked retinitis pigmentosa (XLRP).
They included 29 males with XLRP and confirmed pathogenic RPGR variants, with a mean age of 31.6 years (range 15-55), across 4 centers in the United States. Participants received a subretinal injection of AGTC-501 (rAAV2tYF-GRK1-RPGR) at doses ranging from 2.48 × 1010 to 1.99 × 1012 vg/eye in 1 eye. Injection sites initially targeted the peripheral retina, transitioning to the macula in later cohorts. Main outcome measures were treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), laboratory parameters, immunological responses, and efficacy evaluated by mesopic microperimetry mean sensitivity.
The results showed that all 29 participants experienced at least 1 TEAE, with 11 (38%) reporting grade 3 TEAEs, 6 participants (21%) experienced at least 1 ocular SAE related to AGTC-501, including retinal detachment (n=4), subcapsular cataract (n=1), and glaucoma (n=1), 2 participants (6.9%) had non-ocular treatment-emergent SAEs. Immunological evaluations did not raise safety concerns, of the 4 participants at the highest dose, 3 exhibited concerning retinal pigment epithelial changes. Among those receiving the highest tolerated dose (6.8 × 1011 vg/eye), half showed a ≥7 dB improvement in ≥5 loci at 24 months.
Investigators concluded the subretinal AGTC-501 was generally well-tolerated, with preliminary efficacy observed at the maximum tolerated dose, but the highest dose showed an unfavorable risk-benefit profile, prompting the decision not to continue its use in future trials.
Source: ajo.com/article/S0002-9394(24)00552-X/abstract
