Avacincaptad Pegol Two-Year GATHER2 Results in Geographic Atrophy

Key Takeaways

• Both year-2 avacincaptad pegol dosing schedules were associated with less geographic atrophy growth than sham at 2 years.
• Patients receiving avacincaptad pegol were rerandomized at month 12 to monthly or every-other-month dosing, and both schedules remained associated with lower growth than sham.
• Year-2 completion counts were 175 with avacincaptad pegol and 184 with sham, while choroidal neovascularization occurred in 11.6% and 9.0%, respectively, with no retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation reported.

In the GATHER2 two-year results, avacincaptad pegol was associated with less geographic atrophy growth than sham at 2 years, including a reported 14% difference with monthly dosing in year 2. The phase 3 randomized sham-controlled study enrolled patients with non-center point-involving geographic atrophy secondary to age-related macular degeneration. Geographic atrophy growth remained reduced through 2 years of follow-up. Year-2 completion data and ocular safety findings were also reported through 2 years.

The phase 3 GATHER2 trial was a randomized, sham-controlled study in patients with non-center point-involving geographic atrophy secondary to age-related macular degeneration. Avacincaptad pegol is a pegylated RNA aptamer that inhibits complement C5, and positive year-1 results had previously been published. During year 1, patients were assigned 1:1 to monthly intravitreal avacincaptad pegol 2 mg or sham. At month 12, prior avacincaptad pegol recipients were rerandomized to every-month or every-other-month dosing for year 2, while sham recipients continued sham.

Exact year-2 efficacy values were reported in the second-year comparison against sham. Mean geographic atrophy area growth from baseline to year 2 was 4.46 mm2 with monthly avacincaptad pegol and 5.18 mm2 with sham, with standard errors of 0.25 and 0.17 mm2, respectively. The absolute difference for monthly dosing was 0.724 mm2, with a 95% confidence interval of 0.133 to 1.315 mm2 and P = 0.0165, representing a 14% difference. For every-other-month dosing, mean growth was 4.20 mm2, with an absolute difference versus sham of 0.976 mm2, a 95% confidence interval of 0.377 to 1.575 mm2, and a nominal P = 0.0015, representing a 19% difference. Both schedules remained associated with reduced geographic atrophy growth versus sham at 2 years.

By year 2, 175 patients in the avacincaptad pegol group and 184 patients in the sham group had completed the study. Over 2 years, choroidal neovascularization in the study eye was reported in 11.6% of all treated avacincaptad pegol patients and 9.0% of sham patients. No retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation was reported during the 2-year period. Investigators indicated that no new safety signals were seen in year 2 compared with year 1.