AAO 2025: Clinical outcomes of early vs delayed pegcetacoplan treatment in GA

In an interview with Esther Lee Kim, MD, from Orange County Retina in California, we discussed the continued study of pegcetacoplan in clinical trials. Kim reviewed key points from the GALE extension study, which provides critical data on tissue preservation and visual function in patients with geographic atrophy. By examining treatment duration, efficacy, and novel measurement techniques, the researchers shed light on the importance of early intervention in managing this progressive eye condition. GA presents nuanced challenges of measuring disease progression. Kim highlights the limitations of traditional visual acuity tests and value microperimetry as a more sensitive diagnostic tool.

Note: The following conversation has been lightly edited for clarity.

Ophthalmology Times: What are the most striking differences in anatomic outcomes (GA lesion growth, photoreceptor preservation) between early versus delayed pegcetacoplan treatment over 48 months, and how do you interpret their clinical relevance?

Esther Lee Kim, MD: The GALE extension study was very interesting because it gave us a chance to see how patients who were in the sham arm, but were eventually crossed over to treatment at 24 months did, and we can see that in those patients who were crossed over who received therapy for the same duration, so for 24 months, there was 1.11 mm2 of tissue saved. Whereas in the treated eye, so the patients who were enrolled in the study from the get go, therefore receiving 48 months of treatment, had 3.16 mm2 of tissue preservation. So in other words, patients had received twice the duration of therapy saw a nearly 3-fold increase in the amount of tissue preservation. To me, this really resonates with the drum that we've sort of been beating, where earlier treatment does lead to better outcomes, and I feel like this gives us tangible benchmarks to see how that difference actually plays out in clinical trials.

OT: Were there any notable differences in safety events or adverse outcomes (such as conversion to neovascular AMD, intraocular inflammation, or other risks) between early and delayed treatment arms, and how should those influence clinical decision-making on timing of therapy?

Kim: So safety is paramount, and we are looking very fastidiously at that, and Apellis has done a great job in being transparent. There were no additional or new safety signals in the GALE extension studies with those seen in OAKS and DERBY, the pivotal phase 3 trials.

What's great about the pegcetacoplan studies is we're going to have five years worth of data, which is the largest database of GA trials. This really has allowed us to learn more about GA as a disease entity, in terms of even understanding natural progression, the way those sham patients progress. I think it just provides us with a holistic view. I think what's good to keep in mind moving forward is, in a nutshell, we haven't seen any new safety signals, be it in clinical trials or even in real world, but we do see this increasing, continuous efficacy over time, with those being treated earlier, seeing the greatest benefit.

OT: How did the functional vision endpoints (visual acuity decline, microperimetry sensitivity, progression of scotomas) differ between the early-treatment and delayed-treatment cohorts, and which endpoints do you consider most meaningful?

Kim: So we all know that BCVA is a poor marker of GA lesion growth. In fact, when you look at all the different metrics, the NEI visual function questionnaire, low luminance, VA, etc, those all have poor correlation, and in fact, BCVA has the worst correlation to GA lesion growth. What has the best of what we have so far is microperimetry, which is basically like a visual field test of the macula. So patient reported perception of light at various light intensities. What we see with the microperimetry data with pegcetoplan, so even starting from 12 months, we see a difference in those treated patients having fewer scotomatas points, both at the central 4-points and then the central 16-points, but at 36 months, this difference actually becomes clinically significant. So we do see a visual functional benefit in patients who are being treated with pegceoplan.