At the 2024 American Academy of Ophthalmology (AAO) meeting in Chicago, Dilsher S. Dhoot, MD, presented a subset of data from the GALE open-label extension study (NCT04770545), focusing on the anatomical and visual function outcomes of 36 months of continuous pegcetacoplan treatment for patients with subfoveal geographic atrophy (GA) (Syfovre; Apellis). “Pegcetacoplan is the only FDA-approved therapy to demonstrate efficacy in subfoveal GA, with increasing efficacy that’s been seen over 36 months,” said Dr. Dhoot. “Pegcetacoplan has also shown a visual function benefit in subfoveal GA as demonstrated on microperimetry.”
The full 36-month dataset from GALE was discussed in Retinal Physician’s Clinical Trial Download column earlier this year. Read more here.
In the original 2-year OAKS and DERBY trials, which led to US Food and Drug Administration (FDA) approval of pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration, 65% of patients had subfoveal GA, said Dr. Dhoot. He noted that although subfoveal GA usually results in greater vision loss as lesions extend into the fovea, affecting central vision, these patients can still benefit from treatment. “22% of these patients had vision that was better than 65 letters, which is 20/50,” he said. “There’s vision on the table that can be saved.” Many of these patients that completed OAKS and DERBY (83%) continued into the GALE open-label extension study for additional treatment, he said, with pegcetacoplan injections administered monthly or every other month.
In year 3, the reduction in GA growth was 35% in the overall GALE population, with increasing effects over time, said Dr. Dhoot, while in the subfoveal subgroup the reduction was 31%. “There’s certainly meaningful retinal tissue that’s preserved in these subfoveal patients by month 36 — 1.1 mm2 in the monthly group, 0.98 mm2 in the every-other-month group,” said Dr. Dhoot. “This is meaningful, functional tissue that’s saved in increasing amounts over time.”
Microperimetry provides insight into the visual function benefit of treatment for patients with subfoveal GA, as these patients showed fewer new scotomatous points compared to sham crossover through month 36. “This becomes statistically significant by month 24 and into month 36, so less new scotomatous points,” said Dr. Dhoot. Post hoc analyses of the data showed that patients receiving pegcetacoplan had demonstrated up to a 32% and 54% risk reduction in developing an absolute scotoma of the central 4 (equivalent to the central subfield) and central 16 macular loci, respectively, he said.
Figure 1. Images from a 68-year-old patient with bilaterial subfoveal geographic atrophy secondary to age-related macular degeneration at baseline and after 3 years of treatment with pegcetacoplan. Best-corrected visual acuity remained stable in the treated eye, but declined sharply in the untreated fellow eye. The patient was treated for 2 years in the DERBY trial, and continued treatment in the first year of the GALE open-label extension. Image courtesy Dilsher S. Dhoot, MD.
Dr. Dhoot concluded his presentation with a case example of a patient with bilateral subfoveal GA. “The study eye being treated with pegcetacoplan progresses, but to a much lesser degree (29%) than the untreated fellow eye (88%),” he said (Figure 1). “This is just one case, but it’s a striking case.” Dr. Dhoot’s presentation occurred during the late-breaking developments session of Friday’s Retina Subspecialty Day program. RP
