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The earlier patients with potentially blinding geographic atrophy start treatment with the complement inhibitor pegcetacoplan, the more retinal tissue they retain 4 years later compared with patients who waited 2 years to begin therapy, an extension trial of pivotal phase 3 trials found. 

“The application of these findings is, if you have patients in the clinic that have geographic atrophy, clinicians a lot of times will delay treatment and wait 6 months,” Dilsher Dhoot, MD, retina specialist at California Retina Consultants in central California, told Medscape Medical News after presenting the results of the GALE extension study at the European Society of Retina Specialists (EURETINA) 2025 in Paris, France. “This is giving the clinician evidence that delaying treatment by large amounts of time may ultimately result in less benefit to the patient.”

Patients who started pegcetacoplan on enrollment in the OAKS and DERBY phase 3 trials and continued with treatments through 48 months into the GALE study retained up to three times more tissue than patients who were in the sham group of the phase 3 trials, who did not receive the drug and then crossed over 24 months later to pegcetacoplan treatment upon entering the GALE study.

Study Results

In OAKS and DERBY, compared with sham patients, patients who received monthly and every-other-month treatment with pegcetacoplan experienced reductions in the growth of geographic atrophy of 19% and 18%, respectively, Dhoot told attendees. “In the second 24 months, you can see a 28% reduction in both groups relative to the projected sham,” he said.

Patients with lesions not in the fovea — the central part of the macula in the back of the eye that has the greatest concentration of rods and cones and produces the sharpest vision — experienced the greatest benefits, Dhoot said. Compared with the sham patients, the monthly and every-other-month pegcetacoplan groups showed 27% and 24% reductions in lesion growth during the first 24 months and 36% and 30% reductions during the second 24 months, respectively.

“What does this decrease in lesion growth rate really represent? Well, it represents tissue,” Dhoot told attendees at the meeting. That translates into up to 3.16 mm² more tissue preserved in the monthly group and up to 2.7 mm² more in the every-other-month group at 48 months. By comparison, patients who started pegcetacoplan treatment later had 1.11 mm² of tissue preserved at 48 months, he said — a difference he termed “significant enough.”

Safety outcomes in the extension study were consistent with the pivotal trials, Dhoot said. In patients treated with monthly pegcetacoplan through 48 months, the overall rate of infectious endophthalmitis was 1.2% and that of intraocular inflammation was 4.8%. In the every-other-month patients, those rates were 0.4% and 1.1%, respectively. 

“It makes intuitive sense that earlier treatment results in better long-term results for the health of the patient,” Dhoot told Medscape Medical News.

The GALE study’s key finding “is not a surprising result given the longer time of exposure for the patients treated in the parent studies,” David Eichenbaum, MD, retina specialist with Retina Vitreous Associates of Florida in Tampa, Florida, told Medscape Medical News. 

“This study emphasizes the improved tissue preservation and relative benefit in starting patients on geographic atrophy therapy earlier in their disease course,” he said. 

Using data collected from prospective clinical trials is a “relative strength” of the study, Eichenbaum added.

The studies were funded by Apellis Pharmaceuticals. Dhoot reported serving as a consultant to Apellis Pharmaceuticals and Astellas Pharma. Eichenbaum disclosed having financial relationships with Apellis Pharmaceuticals.

Richard Mark Kirkner is a medical journalist based in Philadelphia.