Study Indicates Who May Benefit Most From GA Treatment

A real-world retrospective study has shown that patients experiencing progressive daily vision loss from geographic atrophy (GA), a late form of nonexudative age-related macular degeneration, may derive the most benefit from the complement inhibitor pegcetacoplan, which the US Food and Drug Administration (FDA) last year approved as the first treatment for the condition. 

The study, which treated 147 eyes from 110 patients with symptomatic vision loss, found that treatment with monthly pegcetacoplan (Syfovre, Apellis Pharmaceuticals) slowed the annualized growth rate of GA lesions by 41% on average, lead investigator Philip Rosenfeld, MD, PhD, reported at EURETINA 2024. That rate is more than twice that reported from the combined results after 1 year in the pivotal clinical trials. 

“For the first year, we tried to keep the injections to every 4-5 weeks, but we have dosing flexibility with Syfovre, and injections can be spaced out to every 8 weeks as shown in the clinical study,” said Rosenfeld, a retina specialist at Bascom Palmer Eye Institute, part of the University of Miami.

“These results are very significant because they show us how we really can use the drug in patients in the real world, and that we’re really going to have the potential to have a significant slowing of the growth rate of the lesions,” Anat Loewenstein, MD, chair of ophthalmology at Tel Aviv Medical Center, in Israel, and president of EURETINA, told Medscape Medical News.

Managing Patient Expectations

“Managing expectations is really important in patients with geographic atrophy,” Rosenfeld said during his presentation. He noted that GA from dry age-related macular degeneration differs from the exudative form of the disease, which requires that the treatment should be started as soon as possible once diagnosed. 

“Once GA is diagnosed, we have some time here, and educating the patient is crucial,” Rosenfeld told Medscape in an interview. “The first thing you have to tell the patient is that their vision will not improve. This is a slowly progressive disease, and we have time to educate the patient, teach them to check their vision daily at home, and then see them back in a month or more. Many times they call me to report that they are now aware their vision is worse, and they want to start treatment as soon as possible.”

Rosenfeld said the population in the new study differed from those in the phase 3 OAKS and DERBY trials, which included patients with all GA secondary to AMD as long as they met broad inclusion and exclusion criteria designed to recruit a “generalizable” population. However, his study included only patients with symptomatic vision loss, along with those who previously had anti–vascular endothelial growth factor (anti-VEGF) injections, who were excluded in the clinical trials. Anti-VEGF therapy is indicated for periodic treatment of the wet form of age-related macular degeneration. 

The OAKS trial reported that pegcetacoplan slowed the growth of GA lesions by 21% after 1 year; in DERBY, treatment slowed the growth rate by 12%, which was not statistically significant. 

In Rosenfeld’s study, participants were imaged using optical coherence tomography (OCT) every 3 months for eyes with dry macular neovascularization (MNV) and no previous anti-VEGF injections. Imaging was performed monthly for eyes that had previous anti-VEGF injections or during the study and eyes with treatment-naive nonexudative MNV. The area of GA was measured using en face OCT, a reliable method that is faster and more comfortable for the patient compared with autofluorescence imaging. 

In the 56 eyes with previous annual visits, the growth rate of GA lesions was 0.32 ± 0.22 mm/year before pegcetacoplan treatment and 0.19 ± 0.11 mm/year after, Rosenfeld reported. 

The reduction in lesion growth in treated patients was similar regardless of the location of the lesions, Rosenfeld said, whether subfoveal, in the center of the macula, which is responsible for central vision, or outside the fovea.

“In terms of average best-corrected visual acuity, they started at 63 letters and ended at 59 letters, so there was a loss of four letters,” he said. “As I tell the patients, the disease will still progress, but more slowly with Syfovre injections.”

Twenty-nine eyes (27%) in the study developed exudative age-related macular degeneration, but 19 showed no evidence of MNV, Rosenfeld said. However, 14 eyes (12.8%) in Rosenfeld’s study required anti-VEGF therapy to treat the exudation, a rate similar to the anti-VEGF injection rate reported in OAKS and DERBY. 

Tips for Avoiding Complications 

One case of vitritis was reported in the 147 study eyes, but no cases of noninfectious endophthalmitis or occlusive vasculitis were reported, Rosenfeld said. In 2023, six months after the FDA approved pegcetacoplan, the American Society of Retina Specialists warned its members about cases of vasculitis from the treatment. The lone case of vitritis in Rosenfeld’s study was treated with topical corticosteroids and resolved, he said.

Rosenfeld said very high intraocular pressure after the 10-µL injection plays a role in causing the occlusive vasculitis, and he provided a protocol for making the complication of excessive high pressure after the pegcetacoplan injection a “never event.”

“For me, this is the most important part of the protocol: soaking a cotton-tip swab with lidocaine and pressing on the eye for 20-30 seconds,” he said. “It adds an extra 1-2 minutes to the protocol, and it was done in the clinical trial, but when the drug was FDA-approved and in clinical practice, my colleagues weren’t doing this. It’s a very effective way to lower the intraocular pressure after a large volume is injected.” 

He also recommended using the drug no more than 8 hours after removing it from the refrigerator and using the filtration needle and 29-gauge injection needle that comes in the package.

Loewenstein acknowledged that the results Rosenfeld reported were significantly better than the pivotal clinical trials. “However, I have to mention that the patients that were reported on are patients that are very likely ‘cherry-picked’ — patients that have good compliance and will continue the treatment, she said. “It’s really like having the best ideal patient.” 

That the study included both subfoveal and foveal lesions as well as patients who had previous anti-VEGF therapy “makes it more widely applicable,” she said. 

“It’s important to note that when we start to use a new therapy, we are slowly learning how to use it in addition to the results that we saw in the pivotal trial,” Loewenstein added. “So it’s really crucial to look at what’s happening in the real world; and to me, I learned a lot from this study. I came out very encouraged.” 

Rosenfeld disclosed financial relationships with Apellis Pharmaceuticals and Carl Zeiss Meditec. Loewenstein disclosed financial relationships with Apellis and Astellas Pharma. 

Euretina 2024. Session 10: AMD. Presented Sept. 21, 2024.

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.