Intravitreal pegcetacoplan for retinal tissue preservation in patients with GA

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Pegcetacoplan (Syfovre, Apellis Pharmaceuticals, Inc.) injections appear to be beneficial in saving a large number of retinal pigment epithelial cells (RPE) and photoreceptors in patients with geographic atrophy (GA).

Sunir J. Garg, MD, codirector of retina research at the Wills Eye Hospital , Philadelphia, presented the results on behalf of the OAKS, DERBY, and GALE investigators at the 2023 Annual Meeting of the American Society of Retina Specialists in Seattle, Washington. The findings are extremely important considering the rate at which GA can progress over 2 years, a relatively short period of time when compared with other progressive diseases that affect vision. Garg reported that the progression rate of GA in the study was approximately 4 mm² over 2 years. Pegcetacoplan works in the eye by binding to the complement factors C3 and C3b and regulating the overactive complement system.

GALE Study Results At 30 Months

The phase 3 GALE study (NCT04770545) is an open-label, 36-month extension study of the 2-year OAKS and DERBY trials. The 6-month GALE data were compared with the same treatment regimens from the OAKS and DERBY studies as well as the projected sham in the 6-month GALE study. The goal was to determine the degree of retinal tissue preservation and the number of retinal pigment epithelial (RPE) cells saved.

The GALE study included 780 patients, representing 83% of patients who completed OAKS and DERBY. The patients continued with the same treatment schedule they received in OAKS and DERBY (pegcetacoplan monthly, pegcetacoplan every other month, or sham). Those originally randomly assigned to sham were converted to active treatment in 1 of the 2 dosing regimens.

Garg reported the 30-month data showing that patients receiving pegcetacoplan experienced an increasing treatment effect compared with sham (ie, a decrease in GA lesion area over time). Patients receiving pegcetacoplan monthly had a 24% decrease in lesion size and those treated every other month had a 21% decrease (P < .001 for both comparisons).

RPE CELLS SAVED

The investigators determined the number of affected RPE cells. Garg explained that the normal macular RPE density ranges from 5082 to 7728 cells/mm².

The estimate of cells saved in the monthly pegcetacoplan group ranged from 5900 to 9000 cells/mm², and in group treated every other month the estimate ranged from 5200 to 8000 cells/mm². Pegcetacoplan exhibits an even greater effect on reducing GA lesion progression for lesions outside the fovea. In this subgroup, the number of RPE cells saved ranged from 9800 to 14,800 cells/mm² among patients receiving monthly pegcetacoplan and 8200 to 12,500 cells/mm² in the patients treated every other month.

The take-home messages of the presentation were as follows:

• pegcetacoplan slows GA progression with both monthly and every-other-month dosing;
• pegcetacoplan shows an increasing treatment effect over time; and
• based on the area of retinal tissue preserved, between 8200 to 14800 RPE cells are saved with 2.5 years of treatment, which corresponds with a much larger number of photoreceptor cells saved.

References

Ach T, Huisingh C, McGwin G Jr, et al. Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2014;55(8):4832-4841. doi:10.1167/iovs.14-14802

Bhatia SK, Rashid A, Chrenek MA, et al. Analysis of RPE morphometry in human eyes. Mol Vis. 2016;22:898-916.

Sunir Garg, MD

E: sgarg@midatlanticretina.com

Garg is codirector of retina research at the Wills Eye Hospital in Philadelphia. He is a consult to and member of the advisory board of Apellis Pharmaceuticals and has received research funding from Apellis Pharmaceuticals.