Early Treatment Recommended for Geographic Atrophy, with Roger Goldberg, MD, MBA

Pegcetacoplan has demonstrated long-term efficacy and safety in treating patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD), based on the 48-month results from the GALE open-label extension of the OAKS and DERBY studies.¹

Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, by Roger Goldberg, MD, MBA, Bay Area Retina Associates, this study aimed to determine the impact of early versus delayed treatment with intravitreal (IVT) pegcetacoplan for GA secondary to AMD. Investigators collected data from both the treated and fellow eyes, as well as the location of GA lesions.¹

OAKS and DERBY were the backbone of the US Food and Drug Administration’s (FDA) approval of pegcetacoplan. A group of 1258 patients were randomized to either intravitreal pegcetacoplan 15mg or sham either monthly or every other month for 2 years. These trials initially indicated that both the monthly and EOM dosing of pegcetacoplan slowed GA lesion growth, based on FAF imaging at 24 months.²

Goldberg sat down with HCPLive to discuss the study and his presentation. He noted the long-lasting anatomic benefits shown by pegcetacoplan treatment, indicating both the drug’s efficacy and potential for dose extension.

“What really highlights the need for earlier intervention is that, when we look at the microperimetry data and compare the patients who have been on 4 years of therapy versus sham treatment for 2 years followed by 2 years of active treatment, we see about a 35% risk reduction in the central 4 or central 16 low sight on microperimetry progressing to an absolute scotoma,” Goldberg told HCPLive.

P patients who completed OAKS and DERBY were given the option to continue to the additional 36-month GALE open-label extension. Those in the pegcetacoplan arms continued to receive pegcetacoplan monthly (PM) or pegcetacoplan every other month (PEOM); these arms made up the “Early Treatment” group. The patients from OAKS and DERBY who were receiving sham were crossed over to receive active pegcetacoplan treatment at the same interval; these patients comprised the “Delayed Treatment” group. Patients with both subfoveal (SF) and nonsubfoveal (NSF) GA lesions were enrolled.¹

A total of 83% (n = 782) of patients involved in OAKS and DERBY enrolled in the GALE open-label extension. Of these, 79% (n = 622) of patients enrolled in GALE completed the trial in the first 24 months. Between months 24 and 28, investigators noted a reduction in GA growth versus projected sham in NSF GA by 36% with PM and 30% with PEOM. The overall combined group (PM and PEOM) exhibited a 28% reduction (all P <.001).¹

Eyes in the Early Treatment group demonstrated consistently better outcomes, with GA lesion growth reduced by 22% to preserve 1.1 mm2 of retinal tissue. No events of retinal vasculitis were observed through month 48. Like OAKS and DERBY, reported events of retinal vasculitis in the post-marketing setting were rare (around 1 in 4000), with >510,000 injections administered across the real-world setting and phase 3 programs during 2024 alone.¹

Ultimately, Goldberg and colleagues determined that earlier treatment was largely more effective and beneficial to patients. Goldberg also discussed the risk-benefit ratio inherent to discussions of GA treatment, weighing the frequency of injection against the rapidity of positive outcomes.

“I think a lot of the debate that comes up around treatment of GA is frankly about this risk-benefit ratio, because it is an injection given monthly or every other month,” Goldberg said. “That being said, we now have shown anatomic and functional benefits. Although we’re seeing an increased treatment effect over time, we’re not seeing an increased risk of adverse events over time.”

Editor's Note: Goldberg reports disclosures with Annexon, Apellis, Neurotech, NovoNordisk, Roche/Genentech, Regeneron, and others.

References

1. Golberg R, Singerman L, Dhoot D, Boyer D, Maia A, et al. Early vs Delayed Pegcetacoplan Treatment for GA Secondary to AMD: 48-Month Results From OAKS, DERBY, and GALE Open-Label Extension. Abstract presented at the 43^rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2.

2. Chiang A, Davis M, Stevens W, et al. Visual Acuity and Quality of Life Outcomes With Pegcetacoplan Treatment: A Post Hoc Analysis From the OAKS and DERBY Trials. Am J Ophthalmol. Published online May 29, 2025. doi:10.1016/j.ajo.2025.05.023