Avacincaptad Pegol Shows Two-Year Benefit in Geographic Atrophy

Key Takeaways

• Avacincaptad pegol remained associated with less geographic atrophy growth than sham at 2 years, and both year-2 dosing schedules remained separated from sham.
• Study-eye choroidal neovascularization was reported in 11.6% of avacincaptad pegol-treated eyes and 9.0% of sham-treated eyes over 2 years.
• No retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation were reported over 2 years, and no new safety signals were noted relative to year 1.

Two-year follow-up from the GATHER2 phase 3 trial showed continued slowing of geographic atrophy growth with intravitreal avacincaptad pegol versus sham in non-center point-involving geographic atrophy secondary to age-related macular degeneration, with a 19% difference during year-2 every-other-month dosing.

Eligible patients were randomized 1:1 to monthly avacincaptad pegol 2 mg (n=225) or sham (n=222) for 1 year. At month 12, patients originally assigned to avacincaptad pegol were re-randomized 1:1 to every-month dosing (n=96) or every-other-month dosing (n=93) during year 2. By year 2, 175 patients in the avacincaptad pegol group and 184 in the sham group had completed follow-up.

From baseline to year 2, mean rate of geographic atrophy area growth was 4.46 mm2 with every-month avacincaptad pegol and 5.18 mm2 with sham. The reported difference was 0.724 mm2, with a 95% confidence interval of 0.133 to 1.315 and a P value of 0.0165. That comparison corresponded to a 14% difference versus sham over 2 years. With every-other-month dosing in year 2, mean rate of geographic atrophy area growth was 4.20 mm2, with a difference versus sham of 0.976 mm2, a 95% confidence interval of 0.377 to 1.575, and a nominal P value of 0.0015, representing a 19% difference. The investigators concluded that either year-2 dosing schedule remained associated with reduced geographic atrophy growth versus sham.

Over 2 years, study-eye choroidal neovascularization occurred in 11.6% of avacincaptad pegol-treated eyes and 9.0% of sham-treated eyes. No retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred during the same period. Avacincaptad pegol was described as a pegylated RNA aptamer that inhibits complement C5. Researchers also reported no new safety signals compared with year 1.