Real-World Study Shows Positive Pegcetacoplan Results for Geographic Atrophy

The study, published in American Journal of Ophthalmology, showed pegcetacoplan to be more effective than in the clinical trials. However, study participants experienced significant loss of BCVA and eyes with prior anti-VEGF treatment were more likely to develop exudation. Despite this, the researchers concluded pegcetacoplan to be “safe and effective” in the real-world setting. Photo: Paul Karpecki, OD. Click image to enlarge. The commercial release of complement inhibitors to treat geographic atrophy (GA) has been closely watched and highly anticipated in the eyecare community. The clinical trials of both pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay) showed promising results in the slowing of GA lesion growth, although some safety concerns were noted with pegcetacoplan, specifically retinal occlusive vasculitis and vision loss. Many have wondered how real-world results would compare to these outcomes, and a new study in American Journal of Ophthalmology claims pegcetacoplan is performing better than previous research found.Conducted by a team of doctors from the Bascom Palmer Eye Institute in Miami, this retrospective study included patients diagnosed with symptomatic GA secondary to age-related macular degeneration (AMD). Of the 154 eyes injected, 103 eyes of 76 patients completed one-year follow-up. The mean age of patients was 81 years and 71% were female. GA lesions were graded on en face structural SS-OCT images by identifying the outlines of large choroidal hypertransmission defects (hyperTDs) that appeared as bright regions with a greatest linear dimension (GLD) of at least 250μm. The presence of new-onset exudation was determined using SS-OCT during follow-up visits, and identified as retinal thickening. Each eye received an average of 10 injections, with an interval of 1.2 months between injections. While monthly dosing was the preferred dosing schedule, the package insert allowed for more flexible dosing which was between every four to eight weeks when needed. According to the study results, for the 97 eyes with one year of follow-up and measurable GA, the square-root GA growth rate after pegcetacoplan treatment was 0.24±0.15mm/year. Of these 97 eyes, 63 eyes had prior annual visits before pegcetacoplan treatment was started. In these eyes, the annual GA growth rate was 0.33±022 mm/year before pegcetacoplan and 0.21±0.12 mm/year after treatment, resulting in a 37% decrease in the growth rate. There were no significant differences in GA growth rate between foveal and non-foveal GA, either before or after the use of pegcetacoplan. The mean BCVA declined from 63±14 to 59±15 letters over one year, with no significant difference between foveal and non-foveal GA. Researchers also reported 21% of eyes lost 10 letters or more, and 17% lost 15 letters or more in BCVA. Among the 29 eyes developing exudation during treatment, 66% had no evidence of any detectable MNV at baseline and during treatment on OCT-A. There was a significant difference in the rate of exudation in eyes with previous history of anti-VEGF therapy or nonexudative MNV at baseline compared with those without a history of anti-VEGF therapy or nonexudative MNV (70% vs. 18%).“A possible mechanism for this pegcetacoplan-associated exudation without detectable MNV could be the activation and repolarization of inflammatory macrophages, resulting in VEGF production,” wrote the researchers in their paper. “In addition, exudation during the pegcetacoplan treatment was reported previously to be associated with baseline double-layer sign, suggestive of nonexudative MNV in the study eye. The same proposed mechanism of pegcetacoplan-induced VEGF production could be responsible for the activation of these non-exudative MNV to become exudative MNV.”There was a mean difference of 0.09mm/year (95%) between eyes without and with prior anti-VEGF therapy. Six of these eyes had a prior annual visit before treatment. The annual GA growth rate was 0.27± 0.25mm/year before treatment and 0.15±0.11 mm/year after—a 44% decrease in the growth rate. The authors point out in the paper that their results appear better than those of the two large, 24-month Phase III FDA trials of pegcetacoplan and the GALE extension study, which recently reported an overall 24% slowing of GA growth after four years of therapy.Previous studies reported that pegcetacoplan seemed to demonstrate greater efficacy in patients with non-foveal GA lesions at baseline compared with foveal GA. The present work showed a comparable decreases in the growth of both foveal (37%) and non-foveal GA (38%) after treatment. “While our inability to detect a statistically significant difference may be explained by our much smaller sample size,” they wrote, “another possible explanation for our greater treatment effects and the similarity in responses between foveal and non-foveal GA may be that we only treated patients who reported to be symptomatic and actively losing vision over one to three months in their eyes prior to injection.”They continued, noting that two different strategies were used to calculate the percentage decrease in GA growth rate following pegcetacoplan therapy. The first was similar to that used in clinical trials, which involved calculating the group average square-root GA growth rate before and after treatment. This yielded the 37% decrease in GA growth. The second strategy used longitudinal data for each individual patient, calculating the percentage change for each eye individually and then averaging these percentages across the cohort. This results in only a 29% reduction in GA growth, the authors explained.The small sample size and the limited number of eyes with nonexudative MNV or prior anti-VEGF therapy at baseline are potential limitations, according to the researchers. They plan to continue studies with other imaging biomarkers and longer follow-up time. Ultimately, the authors concluded that “pegcetacoplan therapy appears to be both effective and safe for the treatment of GA in a real-world setting.”Click here for the journal source. Shen, Mengxi et al. Real-world experience with intravitreal pegcetacoplan for the treatment of geographic atrophy in age-related macular degeneration. American Journal of Ophthalmology. September 4, 2025. [Epub ahead of print.]This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.