Pegcetacoplan Reduces Rate of Geographic Atrophy Growth, 1-Year Trial Data Shows

12-month results from the ongoing GALE open-label extension study have indicated that pegcetacoplan successfully reduced the mean rate of geographic atrophy (GA) growth with increasing efficacy.

GALE was initiated in response to the results from the 24-month OAKS and DERBY trials, both of which were multicenter, randomized, double-masked, sham-controlled phase 3 studies. OAKS and DERBY both examined 1258 patients ≥60 years with GA secondary to age-related macular degeneration.2

Patients were randomized in a 2:2:1:1 ratio to intravitreal 15 mg per 0-1 mL pegcetacoplan monthly, or every other month, or to sham monthly or every other month. Results of OAKS indicated that pegcetacoplan significantly slowed GA lesion growth by 21%, while DERBY exhibited the same, but without significance at 12%.2

“When fully completed, the GALE long-term extension study will cover 36 months in addition to the previous 24 months of OAKS and DERBY, yielding 5 total prospective years of data for pegcetacoplan treatment of GA in AMD,” wrote Charles C. Wykoff, MD, PhD, Blanton Eye Institute, Houston Methodist Hospital, and colleagues. “Herein, the first-year results from GALE are reported, including safety and efficacy outcomes encompassing up to 36 total months of continuous pegcetacoplan treatment.”1

Wykoff and colleagues administered 15 mg/0.1 mL intravitreal pegcetacoplan either monthly (PM) or every other month (PEOM) to the study eye of all participants in GALE. Additionally, patients from OAKS and DERBY who had been administered PM or PEOM continued the same treatment (PM-PM and PEOM-PEOM), and those who had been given sham were transitioned to pegcetacoplan (SM-PM and SEOM-PEOM). A projected sham, calculated from the prior 24-month GA growth rate of sham patients in OAKS and DERBY, was used as the comparator for GALE.1

Of the 792 patients who enrolled, 790 were included in the safety population and 780 in the modified full analysis set. During the first 12 months, 6305 pegcetacoplan injections were administered – 88.1% of patients (696/790) received ≥75% of planned injections, defined as ≥9 of 12 in PM-PM and SM-PM groups and 5 of 6 in the PEOM-PEOM and SEOM-PEOM groups.1

The team indicated that 727 of 790 patients (92%) completed the first 12 months of treatment; those who discontinued did so due to withdrawal of consent (n = 26), death (n = 21), adverse events (n = 11), loss to follow-up (n = 4), and physician’s decision (n = 1). The most common treatment-emergent adverse events, which were defined as occurring in ≥5% of patients in ≥1 treatment group, included vitreous floaters, ocular discomfort, new-onset eAMD, increased intraocular pressure, conjunctival hemorrhage, cataract, blepharitis, posterior capsule opacification, and retinal hemorrhage.1

During the first 12 months, 1.9% of patients experienced IOI, which occurred in 2.4% of the PM-PM group, 3.9% of the SM-PM group, 0.7% of the PEOM-PEOM group, and 1.4% of the SEOM-PEOM group. Most were treated with topical steroids.1

Investigators noted that in all eyes, including those with nonsubfoveal and subfoveal GA, pegcetacoplan reduced mean change in GA up to 32% vs projected sham. Additionally, over the course of the trial, an 18% reduction in new scotomatous points (P = .0156) was observed within PM-PM, highlighting a significant impact in a prespecified microperimetry analysis. The safety profile of pegcetacoplan in the first 12 months of GALE was also consistent with the OAKS and DERBY trials.1

“The findings from 12 months of open-label pegcetacoplan treatment in GALE build upon the findings of the preceding phase 3 clinical trials (OAKS and DERBY) and the 6-month interim analysis of GALE and provide growing evidence for the long-term safety and efficacy of pegcetacoplan for the treatment of GA,” Wykoff and colleagues wrote.1

References

1. 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. American Journal of Ophthalmology. Published online April 23, 2025. doi:10.1016/j.ajo.2025.04.016

2. Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434-1448. doi:10.1016/S0140-6736(23)01520-9