Pegcetacoplan Demonstrated Increasing Efficacy Through 36 Months

The result of fewer new scotomatous points on microperimetry represents the first time a GA treatment has demonstrated a functional benefit in a prespecified analysis and supports the hypothesis that the retinal tissue preserved is functional tissue. Photo: Wendy Harrison, OD, PhD, and Joe Wheat, OD, PhD. Click image to enlarge. Following years of research on geographic atrophy (GA) and other forms of age-related macular degeneration (AMD), intravitreal pegcetacoplan became the first US Food and Drug Administration (FDA)-approved treatment for GA in February 2023. When fully completed, the GALE long-term extension study will cover 36 months, in addition to the previous 24 months conducted in the OAKS and DERBY studies, yielding five total prospective years of data for pegcetacoplan treatment of GA in AMD. In a recent paper published in American Journal of Ophthalmology, the first-year results from GALE are reported, including safety and efficacy outcomes encompassing up to 36 total months of continuous pegcetacoplan treatment. Pegcetacoplan reduced the rate of GA growth in a heterogeneous GA population over approximately three total years of treatment, with increasing treatment effects over time, and was well tolerated overall. While the efficacy of pegcetacoplan and its effect on retinal tissue preservation were most notable among patients with nonsubfoveal GA, it effectively slowed disease progression among eyes with both nonsubfoveal and subfoveal GA with as few as six injections per year.GALE is a prospective, 36-month, Phase III, open-label extension study following the 24-month OAKS and DERBY trials, evaluating the long-term safety and efficacy of pegcetacoplan in GA. Prespecified microperimetry analysis, including the total number of scotomatous points, was also performed in the OAKS population that rolled over into GALE. Pegcetacoplan was administered monthly or every other month to all study eyes in GALE. Eyes receiving pegcetacoplan in OAKS and DERBY continued the same regimen, while eyes observed with sham in OAKS and DERBY crossed over to receive pegcetacoplan at the same dosing interval in GALE.Through the first 12 months of GALE, 92.0% 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% vs. 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 monthly group compared with projected sham in the first year of GALE. An 18% reduction in new scotomatous points was observed with the monthly administration group 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), one (0.1%) ischemic optic neuropathy, and one (0.1%) infectious endophthalmitis. No events of vasculitis were reported.“This unique data set of GALE afforded the opportunity to assess the treatment effect of pegcetacoplan with an internal control and confirm that clinically meaningful reductions in GA area growth rate (19%) can still be achieved with pegcetacoplan treatment even after two years of unimpeded GA progression and notably large lesion sizes (∼12 mm2) at treatment initiation,” the study authors wrote in their paper.The combined data represented the largest and longest study of a GA treatment to date, with a total of 18,025 pegcetacoplan injections administered over 36 months in Phase III trials. “Pegcetacoplan is the first and only treatment in GA to successfully demonstrate a functional benefit in a prespecified analysis,” the researchers added. Click here for the journal source.  Wykoff CC, Holz FG, Chiang A, et al. Pegcetacoplan treatment for geographic atrophy in age-related macular degeneration over 36 months: Data From OAKS, DERBY and GALE. Am J Ophthalmol. April 23, 2025. [Epub ahead of print].