Avacincaptad Pegol for Geographic Atrophy Secondary to Age-Related Macular Degeneration

Purpose Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2 mg was investigated in GATHER2, with positive year 1 results published. Herein, 2-year results are reported. Design Phase 3, randomized, sham-controlled study ( ClinicalTrials.gov identifier, NCT04435366). Participants Patients with non–center point-involving geographic atrophy (GA). Methods Eligible patients were randomized 1:1 to receive monthly ACP 2 mg (n = 225) or sham (n = 222) for 1 year. At month 12, patients who received ACP 2 mg were randomized again 1:1 to dosing every month (EM; n = 96) or every other month (EOM; n = 93) with ACP 2 mg. Patients who had received monthly sham continued with sham (n = 203). Main Outcome Measures The safety and efficacy of ACP versus sham administration over 2 years and the effect of ACP EM or EOM dosing in year 2. Results Overall, 175 and 184 patients in the ACP and sham group completed the study at year 2, respectively. At 2 years, treatment with ACP demonstrated a continued reduction in GA growth (slope) with both ACP EM and EOM versus sham. From baseline to year 2, the mean rate of GA area growth was 4.46 mm² (standard error [SE], 0.25 mm²) with ACP EM and 5.18 mm² (SE, 0.17 mm²) with sham, a difference in growth of 0.724 mm² (95% confidence interval [CI], 0.133–1.315 mm²; P = 0.0165), representing a 14% difference. From baseline to year 2, the mean rate of GA area growth was 4.20 mm² (SE, 0.25 mm²) with ACP EOM, a difference in growth of 0.976 mm² (95% CI, 0.377–1.575 mm²; nominal P = 0.0015) versus sham, representing a 19% difference. The incidence of choroidal neovascularization (study eye) was 11.6% with ACP (all treated) versus 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 2 mg, either EM or EOM, continued to reduce GA growth versus sham therapy over 2 years with no new safety signals compared with year 1. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.