Real-World Safety of Intravitreal Complement Inhibitor Avacincaptad Pegol for Geographic Atrophy

Purpose: To evaluate the real-world ocular safety profile of intravitreal (IVT) avacincaptad pegol for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods: This retrospective study evaluated eyes with GA secondary to AMD, including those with concurrent neovascular AMD (nAMD) treated with avacincaptad pegol. Conversion (new-onset nAMD) and reactivation (>1 year treatment-free quiescence) were defined as exudation requiring antivascular endothelial growth factor (anti-VEGF) treatment. Demographics, treatment characteristics, visual acuity (VA), intraocular pressure, and adverse events were assessed. Results: Overall, 845 eyes of 590 patients (mean age, 81.8 ± 7.6 years; 71.9% female) received 5608 avacincaptad pegol injections. The mean injection interval was 53.7 ± 22.5 days, with a mean follow-up of 304 ± 173 days. Intraocular inflammation and endophthalmitis rates were low (1 eye each; 0.02% per injection). Conversion occurred in 21 of 590 at-risk eyes (3.6%; 4.3% annualized) after a median of 3 injections (interquartile range, 3-5; range, 1-22). At baseline, nAMD was present in 25.1% of fellow eyes but accounted for 38.1% of conversions, reflecting a higher subgroup conversion rate of 5.4% (6.7% annualized). Among 26 eyes with quiescent nAMD, reactivation occurred in 1 eye (3.8%) after a treatment-free interval of 7.5 years. For eyes requiring concurrent therapy, anti-VEGF treatment intervals remained unchanged. VA remained largely stable (+0.03 logMAR). Persistent ocular hypertension occurred in 8 eyes (1.0%), with no ischemic optic neuropathy or retinal vasculitis observed. Conclusions: In this real-world cohort, a favorable safety profile was found with avacincaptad pegol, with low rates of inflammatory events, endophthalmitis, persistent ocular hypertension, and nAMD conversion, providing clinically relevant data to inform patient counseling and monitoring.