GALE: Pegcetacoplan Proves Long-Term Efficacy in GA, With Esther Kim, MD

Pegcetacoplan has demonstrated its long-term efficacy and safety in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD), with new data from the 48-month GALE extension study supporting earlier treatment.1

GALE, a 48-month phase 3, open-label, multicenter extension study, was conducted after the conclusion of the OAKS and DERBY trials. Each of these trials was a 24-month, multicenter, randomized, double-masked, sham-controlled, phase 3 study, enrolling patients aged ≥60 years with GA secondary to AMD. Investigators in OAKS and DERBY randomly assigned a total of 1258 patients to intravitreal 15 mg per 0.1 mL pegcetacoplan monthly or every other month, or sham monthly or every other month.2

Patients who had completed the 24-month treatment in OAKS or DERBY could enroll in GALE. Those in the pegcetacoplan arm were reassigned to the Early Treatment group and continued the same dose regimen in GALE, while the sham group was reassigned to the Delayed Treatment group and was switched to active pegcetacoplan.1

The editorial team at HCPLive sat down with Esther Kim, MD, a retina fellow at Orange County Retina, to discuss the results from GALE and how they will impact GA care at large.

“We’ve heard the refrain a lot: the earlier the treatment, the better the outcomes. But I think this study actually puts that to the test,” Kim told HCPLive. “We saw that, with 2 times the treatment duration, the study actually had about 3 times the amount of tissue preservation, which really underscores the fact that we see a greater amount of preservation with earlier treatment.”

A collective 83% of the patients from OAKS and DERBY entered GALE. The first 24 months of treatment saw pegcetacoplan reduce GA growth versus projected sham by 36% in the monthly group and 30% in the every other month group in nonsubfoveal GA. Growth was reduced by 28% in the overall population, which included patients with both nonsubfoveal and subfoveal GA.1

By month 48, the Early Treatment group exhibited superior outcomes, with 3.16 mm2 of retinal tissue preserved versus 1.1 mm2 with Delayed Treatment. The safety profile was consistent with that of OAKS/DERBY, and investigators reported no study events of vasculitis.1

Ultimately, Kim and colleagues highlighted more functional macula preserved in the Early Treatment group, as well as 1.5 disc areas of retina preserved after 48 months of treatment. Over the course of the study, >702,000 injections of pegcetacoplan were administered; 118,000 of these were first injections in real-world settings. This allowed investigators to note the relative lack of vasculitis responses at first injection.1

Kim also discussed how these data highlight a gradual shift towards more active treatment, as the lasting improvements in the Early Treatment group exhibit the benefits of administering treatment sooner.

“It would be hard to convince a patient when there’s just a few tiny lesions out in the periphery – in those cases, I think watchful waiting would be prudent,” Kim told HCPLive. “But if patients have larger lesions, are early symptomatic, have lost vision due to GA lesions, have a demonstrative rate of lesion growth, I think those are the patients that we should start treatment early on, almost ASAP, the sooner the better.”

References

1. Kim L, MacCumber M, Dhoot D, et al. Clinical Outcomes of Early vs. Delayed Pegcetacoplan Treatment in GA: 48-Month Results from OAKS, DERBY and GALE. Presented at the American Academy of Ophthalmology 2025 Annual Meeting. Orlando, FL, October 18-20, 2025.

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