Real-world experience with intravitreal pegcetacoplan for the treatment of GA

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Reviewed by Philip J. Rosenfeld, MD, PhD

Philip J. Rosenfeld, MD, PhD, Professor of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, reported the real-world performance of pegcetacoplan (Syfovre, Apellis Pharmaceuticals) in patients with geography atrophy (GA) at the Clinical Trials at the Summit 2024 annual meeting on June 8, in Park City, Utah. A top-line finding was that pegcetacoplan reduced the annualized growth rate of GA by about 41% over 9 months of therapy.

This retrospective real-world evaluation of the drug considered a number of important as-yet-unanswered questions, such as determination of the best patients to treat, the response to pegcetacoplan by eyes with macular atrophy previously treated with anti-vascular endothelial growth factor (VEGF) drugs, the response to pegcetacoplan by non-exudative macular neovascularization (MNV) at baseline, and if all pegcetacoplan-associated exudation was related to MNV and if anti-VEGF therapy is required.

Retrospective analysis

All included eyes (135 eyes of 105 patients treated from 4/12/2023 to 4/23/2024, 962 injections) had symptomatic GA secondary to age-related macular degeneration (AMD) that had initially been treated monthly with 15 mg of intravitreal pegcetacoplan. Swept-source optical coherence tomography angiography (OCTA) measured the GA lesion sizes and determined the presence of non-exudative MNV, and onset and progression of exudation. The growth rate of GA and the best-corrected visual acuity (BCVA) were assessed at 6 and 9 months, Rosenfeld recounted.

The mean baseline patient age was 81 ± 8 years, of whom 72% were women. The mean BCVA at baseline (Early Treatment Diabetic Retinopathy Study equivalent letters) in the study and fellow eyes, respectively, were 63 ± 13 letters (~Snellen: 20/60) and 52 ± 25 letters (~Snellen 20/100). Twelve eyes (10 patients) had been treated previously with anti-VEGF therapy; 9 eyes (9 patients) had non-exudative MNV at baseline.

6-month GA growth rate

In the 101 eyes (75 patients) with a minimal 6-month follow-up, the square-root GA growth rate after pegcetacoplan treatment was 0.24 ± 0.15 mm/year; in 63 eyes with prior annual visits, the respective square-root GA growth rates before and after pegcetacoplan were 0.33 ± 0.22 mm/year and 0.20 ± 0.12 mm/year. Rosenfeld reported that the growth rate decreased by 39% (p<0.001).

9-month GA growth rate

In 74 eyes (58 patients) with a minimal 9-month follow-up, the square-root GA growth rate after pegcetacoplan treatment was 0.21 ± 0.13 mm/year. In the 49 eyes with prior annual visits, the respective square-root GA growth rates before and after pegcetacoplan were 0.32 ± 0.22 mm/year and 0.19 ± 0.11 mm/year. Rosenfeld reported that the growth rate decreased by 41% (p<0.001).

Real-world observations

Exudation seemed to be the major side effect of pegcetacplan and developed in 23% of all 101 eyes following an average of 6 injections.

Regarding safety, vitritis developed in 1 eye (1%); steroid treatmentresulted in a BCVA return to baseline.

Disc edema developed in 3 eyes (3%), the BCVA remained stable, and pegcetacoplan therapy was continued.

No cases of infectious or non-infectious endophthalmitis or occlusive vasculitis developed.

Take-Home Messages

• Pegcetacoplan effectively reduced the annualized growth rate of GA by about 41% at 9 months.
• Exudation associated with pegcetacoplan developed in 23 eyes (23%) over a mean period of 9 months, but only 11 eyes (11%) required anti-VEGF therapy.
• Most exudation was not due to MNV as documented by swept-source OCTA.
• OCT macular thickness maps were useful for managing patients with pegcetacoplan-related exudation

Phillip J. Rosenfeld, MD, PhD

E: prosenfeld@med.miami.edu

Rosenfeld is Professor of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami.He has a financial interest in this subject matter. Rosenfeld is an advisor for Apellis and holds equity in Apellis.

Presentation

Rosenfeld PJ. Real-World Experience with Intravitreal Pegcetacoplan for the Treatment of GA. Presented at the Clinical Trials 2024 at the Summit; June 9, Park City, Utah. Session: First-Time Results of Clinical Trials