Patients with noncentre point-involving geographic atrophy (GA) who receive avacincaptad pegol (ACP) 2 mg every month (EM) or every other month (EOM) show a persistent decrease in GA growth over 2 years relative to sham therapy, with no new safety signals, according to the GATHER2 study.
“Although this study was not designed or powered to compare ACP 2 mg EOM versus EM and no formal test was performed, both ACP 2 mg EM and EOM were effective at slowing the progression of disease relative to sham administration,” the investigators said.
In this phase III trial, eligible patients were randomly assigned 1:1 to receive monthly ACP 2 mg (n=225) or sham (n=222) for 1 year. At month 12, those who received ACP 2 mg were again randomized 1:1 to dosing EM (n=96) or EOM (n=93). The sham group continued to receive monthly sham therapy (n=203).
Overall, 175 patients in the ACP group and 184 in the sham group completed the study. At year 2, treatment with ACP 2 mg either EM or EOM continued reduction in GA growth relative to sham. [Ophthalmology 2026;133:451-465]
The mean rate of GA area growth from baseline to year 2 was 4.46 mm2 with ACP EM compared with 5.18 mm2 with sham. The difference in growth was 0.724 mm2 (95 percent confidence interval [CI], 0.133‒1.315; p=0.0165), representing a 14-percent difference.
In the ACP EOM group, the mean rate of GA area growth from baseline to year 2 was 4.20 mm2, with a difference in growth of 0.976 mm2 (95 percent CI, .377‒1.575; nominal p=0.0015) vs sham, representing a difference of 19 percent.
“The 2-year results from GATHER2 demonstrated the continued safety and tolerability of ACP 2 mg, dosed as either ACP 2 mg EM or EOM in year 2,” the investigators said. “Both doses continued to slow the rate of GA growth versus sham administration.”
Safety profile
No significant difference was noted in the incidence of choroidal neovascularization between the ACP and sham groups over 2 years (11.6 percent vs 9.0 percent). Furthermore, retinal vasculitis, ischaemic optic neuropathy, and serious intraocular inflammation did not occur over 2 years.
“The overall safety profile of ACP 2 mg reported through year 2 was consistent with the safety profile established in year 1, and no new safety signals were identified in year 2 or with flexible dosing,” the investigators said. [Lancet 2023;402:1449-1458]
Two-year treatment with ACP 2 mg was well tolerated, and AEs of special interest were few: one case of nonserious intraocular inflammation, one case of culture-positive endophthalmitis, and no cases of ischaemic optic neuropathy or retinal vasculitis.
The 2-year incidence of serious ocular TEAEs was also low, with one case of subluxated intraocular lens and another of culture-positive endophthalmitis with ACP 2 mg EM.
“The increased incidence of increased IOP is expected with ACP 2 mg because of the intraocular injection volume of 100 μl,” the investigators said. “Overall, serious ocular TEAEs over 2 years were low and comparable between the ACP 2-mg and sham groups (1.8 percent vs 0.9 percent).”