Pegcetacoplan and Monitoring in Geographic Atrophy

Nancy M. Holekamp, MD, FASRS: Although I’m convinced that pegcetacoplan will be safe to give my patients, there’s that rate that shows a higher percentage of patients on treatment with pegcetacoplan developing CNV [choroidal neovascularization], both exudative and nonexudative. That’s fine because we can treat that. But I’m going to have to monitor and get OCT [optical coherence tomography] scans. At first, I thought I’d be putting people on an injection schedule, and they would come in and get their injection. But with this small rate, which is almost double digits at 24 months, we’d need to monitor patients. What’s the monitoring going to be with these injections? It’s not going to be quite like AMD [age-related macular degeneration], for which you use that monitoring to establish your interval. These people are in a set interval, but we’re going to have to monitor. David, what’s your plan for that?

David R. Lally, MD: It’s a critical question that we’re all thinking about, with higher rates of corneal neovascularization—up to the double digits 2 years out. That’s roughly 1 of 10 of our patients within 2 years will who develop that. It comes down to monitoring, which is going to be critically important, so we must follow these patients carefully. You must get the OCT each time they come in because of that risk. In the sham group, they also developed corneal neovascularization as part of natural history, but the rate is higher in the treated group. the OCT monitoring will be critical to watch carefully and pick it up. Hopefully, because we’re monitoring carefully, we can identify it and treat early. These therapies for treating wet [age-related] macular degeneration are outstanding for treating the disease. We have good tools to treat the disease. If we don’t treat GA [geographic atrophy], we know what happens. There’s almost a 100% chance it relentlessly progresses.

The other thing that’s important is looking in these clinical trials at the long-term outcomes of these patients who develop corneal neovascularization. Are they going to respond the same way as a patient not receiving these types of GA therapies? Will they have the same types of outcomes with their wet AMD treatment, or are they going to be different? I’m looking forward to looking at those patients who developed corneal neovascularization in these trials to see what their final visual outcomes were. Because these patients continued to receive the therapy—at least the majority of them did in the pegcetacoplan trials—and were treated on label and with aggressive anti-VEGF therapy.

Jayanth Sridhar, MD: I love your points and how you said pathologic and nonpathologic corneal neovascular membranes. Our understanding of CNVM [choroidal neovascular membrane] has changed. As it changes and evolves, it’s gotten murkier. Are some of these CNVM potentially protective? Some of them need treatment, but some of them probably don’t. How do we make that decision tree going forward? CNVM understanding has improved with OCT angiography and other imaging modalities. We may not need to treat all these patients, but we need to monitor them for exudative damage to the retina. That will be 1 of the components of this: are some of these patients about CNVM? Is that part of the process of this complement inhibitor preventing atrophy over time? One of the conversations, on the flip side, has been that when patients develop atrophy, when they get anti-VEGF, is that the natural history? Or is that related to excessive CNVM regression over time?

Eleonora M. Lad, MD, PhD: Will you do CTS every month? I was thinking about David’s point and how I’ll manage the patients. We do it every month and every other month, according to their treatment pattern. How about homo CT as a potential optional monitoring? We’re speaking about technology. Hopefully AI [artificial intelligence] will help us. How about homo CT? Are there any other tools we might have in our armamentarium to use in the future?

Jayanth Sridhar, MD: Homo CT is a great technology. This is a great example of where it could be implemented. As you said, it’s not for changing our treatment paradigm. We’re not modifying the treatment they must come to the office for. We’re simply doing monitoring for safety events. That’s what the best application of home OCT could be. The patient won’t have to come in for a treatment based on that OCT unless you see some drastic change that compels you to start anti-VEGF treatment. To Dave’s point, we don’t know how those patients will respond. What’s the best approach for those patients? We’ll have to learn. As you said, we may not have a trial data that answers that question.

Nancy M. Holekamp, MD, FASRS: I want to comment on David’s point about looking at the patients who got CNV in these trials and their final visual acuity outcome. There was a very in-depth post hoc analysis of those patients from the FILLY clinical trial that looked at that in-depth. It showed that their visual acuity was unaffected because they’re being monitored and treated for the CNV. When it comes to FDA approval of a drug, every drug treatment will have adverse effects. But the FDA is interested in mitigation. Is there a way to lessen the risks of that adverse effect? For CNV, we have a good treatment for it.

Transcript edited for clarity