Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 2-year efficacy and safety results from the GATHER2 phase 3 trial.

15/12/2025

Ophthalmology

Authors: Arshad M Khanani, Carl J Danzig, Jeffrey S Heier, Glenn J Jaffe, Peter K Kaiser, David R Lally, Sunil S Patel, Lejla Vajzovic, Christina Y Weng, Hersh Patel, Julie Clark, Dhaval Desai, Don Luo, Erin Henry, Frank G Holz

PURPOSE: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2mg was investigated in GATHER2, with positive Year 1 results published. Here, 2-year results are reported.

DESIGN: Phase 3, 2-year, randomized, double-masked, sham-controlled study (NCT04435366).

PARTICIPANTS: Patients with non-center point-involving geographic atrophy (GA).

METHODS: Eligible patients were randomized 1:1 to monthly ACP 2mg (N=225) or sham (N=222) for 1 year. At Month 12, patients who received ACP 2mg and completed Year 1 were re-randomized 1:1 to monthly (EM; n=96) or every-other-month (EOM; n=93) ACP 2mg. Patients who had received monthly sham continued with sham (n=203).

MAIN OUTCOME MEASURES: To evaluate the safety and efficacy of ACP 2mg vs sham over 2 years, and to assess the effect of ACP 2mg EM or EOM dosing in Year 2.

RESULTS: Overall, 175 and 184 patients in the ACP 2mg and sham group completed the study at Year 2, respectively. At 2 years, treatment with ACP 2mg demonstrated a continued reduction in GA growth (slope) with both ACP 2mg EM and EOM vs sham. From baseline to Year 2, the mean rate of GA area growth was 4.46mm (standard error [SE]: 0.25) with ACP 2mg EM and 5.18mm (SE: 0.17) with sham, a difference in growth of 0.724mm (95% confidence interval [CI]: 0.133,1.315; P=0.0165), representing a 14% difference. From baseline to Year 2, the mean rate of GA area growth was 4.20mm (SE: 0.25) with ACP 2mg EOM, a difference in growth of 0.976mm (95% CI: 0.377,1.575; nominal P=0.0015) vs sham, representing a 19% difference. Over 2 years, ocular treatment-emergent adverse events (study eye) occurred in 64.0% and 48.2% of patients with ACP 2mg (all treated) and sham, respectively. The incidence of choroidal neovascularization (study eye) was 11.6% with ACP 2mg (all treated) vs 9.0% with sham over 2 years. No events of retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred over 2 years.

CONCLUSIONS: Dosing of ACP 2mg, either EM or EOM, continued to reduce GA growth vs sham over 2 years with no new safety signals compared with Year 1.

PMID: 41407269