Pegcetacoplan Treatment for Geographic Atrophy in Age-Related Macular Degeneration Over 36 Months: Data From OAKS, DERBY, and GALE

PURPOSE: To report 12-month results from the GALE open-label extension study (NCT04770545), evaluating up to 36 months of intravitreal pegcetacoplan treatment for geographic atrophy (GA) in age-related macular degeneration (AMD). DESIGN: GALE is a prospective open-label extension study following the 24-month, sham-controlled, phase 3 OAKS (NCT03525613) and DERBY (NCT03525600) studies of pegcetacoplan. PARTICIPANTS: Patients with nonsubfoveal or subfoveal GA who completed OAKS, DERBY, or phase 1b APL2-103 (NCT03777332) studies. METHODS: Pegcetacoplan was administered monthly (PM) or every other month (PEOM) to all study eyes in GALE. Eyes receiving pegcetacoplan in OAKS and DERBY continued the same regimen (PM-PM and PEOM-PEOM), while eyes observed with sham in OAKS and DERBY crossed over to receive pegcetacoplan at the same dosing interval in GALE (SM-PM and SEOM-PEOM). Safety and efficacy through the first 12 months of GALE were assessed, reflecting up to 36 months of continuous pegcetacoplan treatment. MAIN OUTCOME MEASURE: Mean rate of change in GA area, total number of microperimetry scotomatous points, and adverse events. RESULTS: Through the first 12 months of GALE, 92.0% (727/790) patient retention was observed. Across all eyes, including eyes with nonsubfoveal and subfoveal GA, pegcetacoplan reduced the mean rate of change in GA area up to 32% versus projected sham. Year after year, the reductions in the mean rate of change in GA area increased, with up to a 42% reduction observed in eyes with nonsubfoveal GA in the PM-PM group compared with projected sham in the first year of GALE. An 18% reduction in new scotomatous points (P = .0156) was observed with PM-PM at 36 months, highlighting a significant impact in a prespecified microperimetry analysis. Adverse events included 33 (4.5%) eyes with exudative AMD, 15 (1.9%) intraocular inflammation (classified as mild or moderate in severity), 1 (0.1%) ischemic optic neuropathy, and 1 (0.1%) infectious endophthalmitis. No events of vasculitis were reported. CONCLUSION: Over 36 months, pegcetacoplan continued to reduce GA growth with increasing efficacy over time and reduced formation of new scotomatous points. The safety profile of pegcetacoplan in the first 12 months of GALE was consistent with the prior 24-month OAKS and DERBY studies.