Vision Benefits in GA With Complement Inhibitor, Regardless of AMD, Anti-VEGF

MONTREAL — Geographic atrophy (GA) had a similar response to the complement inhibitor pegcetacoplan (Syfovre) whether concurrent with neovascular age-related macular degeneration (nAMD) or alone, data from a retina clinical network showed.

Compared with pretreatment status, the rate of GA progression, reflected in loss of retinal pigment epithelium (RPE), slowed by 23% in eyes with GA alone and 40% in eyes with concurrent nAMD. Photoreceptor (PR) loss also slowed in both types of eyes, but eyes with nAMD had numerically greater protection (-58% vs -41%).

Eyes that progressed more rapidly in the 12 months before initiation of pegcetacoplan remained faster after treatment started but the rate of progression slowed, reported Hasenin Al-khersan, MD, of the Retina Group of Florida in Fort Lauderdale, at the American Society of Retina Specialists (ASRS) meeting.

“We saw that rates of atrophy progression were similar pre-pegcetacoplan treatment in eyes with GA alone and those with GA and neovascular AMD,” said Al-khersan. “Subsequent to the initiation of pegcetacoplan, we see a reduction in photoreceptor and RPE atrophy rates over the 12 months in both cohorts, with larger numerical effects in the combined-disease cohort, indicating that pegcetacoplan reduces atrophy progression in those with neovascular AMD and concurrent atrophy.”

Complementary data came from a second ASRS report, a propensity-matched analysis showing a slower rate of visual acuity decline in eyes treated with pegcetacoplan alone or in addition to anti-VEGF therapy for nAMD.

“This effect was most pronounced in the patients with concurrent neovascular AMD who were also being treated with anti-VEGF therapy,” said Nimesh Patel, MD, of Mass Eye and Ear in Boston. “It was statistically significant at all time points for the concurrent-treatment group. We also saw that fewer patients lost 15 letters with pegcetacoplan treatment than controls and that was regardless of anti-VEGF use. The difference was statistically significant at all time points up to 18 months.”

The two reports followed a previous study representing one of the first attempts to quantify the proportion of patients with GA receiving concurrent treatment for nAMD. Including almost 13,000 treated eyes, the real-world data showed that a fourth of patients received concomitant treatment for GA and nAMD.

Commenting on that data at the 2025 ASRS meeting, Patel said, “This is something we’re going to have to think about, as a field, how we are going to manage these patients. We need more data, but it appears that this is a very safe option.”

Al-khersan reported findings from a study evaluating changes in PR and RPE on optical coherence tomography in routine clinical practice, comparing eyes before and after initiation of pegcetacoplan. He acknowledged that investigators performed the study with the aid of the artificial intelligence platform RetinAI Discovery, which is used primarily in research settings.

The study included 240 eyes with GA only and 257 with GA and concurrent nAMD. The study period encompassed the 12 months before initiation of the complement inhibitor and the first 12 months afterward. Complete data were available for 98 eyes with GA only and 142 with concurrent nAMD.

Baseline RPE and PR lesion size did not differ significantly between the GA-only and GA/nAMD groups (6.7 vs 6.6 mm² and 8.7 vs 9.0 mm², respectively). Annualized RPE loss in the 12-month pretreatment period was similar between the groups (1.53 vs 1.61 mm²). Treatment with pegcetacoplan significantly slowed the rate of loss in both groups (P<0.001), but the effect was greater in the GA/nAMD group (0.96 vs 1.17 mm²).

The annualized pretreatment rate of PR loss was 1.66 mm² in both groups. Treatment with the complement inhibitor significantly slowed the rate of PR loss (P<0.001) but more so in the GA/nAMD group (0.70 vs 0.97 mm²/yr).

Patel and colleagues performed a propensity-matched analysis of data from the Vestrum retina specialists’ database, also aided by Retina AI Discovery. Propensity-score matching included patient age, sex, best-corrected visual acuity, GA lesion size, lesion distance to fovea, and subfoveal involvement.

The analysis included 511 patients treated with pegcetacoplan alone, 564 untreated patients (control), 328 patients who received the complement inhibitor and anti-VEGF therapy, and 394 who received anti-VEGF treatment only. Follow-up continued for 18 months.

Pegcetacoplan alone slowed BCVA deterioration versus the control group (57.9 to 52.1 letters vs 59.9 to 47.0 letters). Patients treated with the complement inhibitor and anti-VEGF therapy had statistically significant (P<0.05) slowing of BCVA loss versus patients treated with anti-VEGF therapy alone (60.9 to 56.9 letters vs 58.6 vs 47.8 letters).

Fewer patients lost ≥15 letters when treated with pegcetacoplan alone or with concurrent anti-VEGF therapy. For the pegcetacoplan-control comparison, rates of ≥15-letter loss were 10.2% versus 16.0% at 6 months (P=0.027), 14.5% versus 26.6% (P=0.003), and 23.5% versus 28.8% (P=0.471). Pegcetacoplan plus anti-VEGF therapy also outperformed anti-VEGF alone at all time points:

• 6 months: 7.9% vs 13.5% (P=0.057)
• 12 months: 11.7% vs 20.9% (P=0.046)
• 18 months: 16.0% vs 33.8% (P=0.021)

“To my knowledge, this is the first study — either real world or clinical trial — to demonstrate a statistically significant visual acuity benefit for patients with geographic atrophy with pegcetacoplan, both geographic atrophy alone and concurrent with neovascular AMD and anti-VEGF,” said Patel.