Post hoc analysis shows how pegcetacoplan may impact RPE atrophy

A new study suggests that pegcetacoplan may delay atrophy of the retinal pigment epithelium and photoreceptors in patients with geographic atrophy. Image credit: ©Bussarin – stock.adobe.com

A new study found evidence that suggested that pegcetacoplan (Syfovre, Apellis Pharmaceuticals) may delay atrophy of the retinal pigment epithelium (RPE) and photoreceptors in patients with geographic atrophy (GA),¹ reported Dun Jack Fu, PhD, from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London. He, along with colleagues from the Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands, and Apellis Pharmaceuticals, Waltham, MA, undertook this post hoc analysis of data from two Phase 3 clinical trials of pegcetacoplan.

Spectral-domain optical coherence tomography (SD-OCT) has been the go-to technology to evaluate GA; however, according to the authors, determining the changes in GA progression, based on the Consensus of Atrophy Meetings (CAM) group, requires manual segmentation of OCT volume scans, which is time consuming, labour-intensive, and limited by interrater variability.^2-4

The authors suggested that the process can be streamlined by using automated image segmentation algorithms. They recently developed a deep-learning based platform that uses CAM-defined OCT features to detect and quantify GA and its components.

This post hoc analysis of the OAKS (NCT03525613) and DERBY (NCT03525600) studies included 11,614 SD-OCT volumes from 936 of the 1,258 participants with GA in the 2 parallel 24-month, randomized, double-masked, Phase 3 studies.

All participants had been treated with pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month.

The primary end point was the least-squares mean change from baseline in area of retinal pigment epithelium (RPE) and outer retinal atrophy in each of the three treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months, Fu and associates explained.

Post hoc analysis findings

Among the 936 participants (mean age, 78.5 years; 60.9% women), the authors reported, “… pegcetacoplan but not sham treatment was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs. sham in the least-squares mean change from the baseline values of RPE and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs. pooled sham at month 24, pegcetacoplan monthly, −0.86 mm2; 95% confidence interval [CI], −1.15 to −0.57; P < 0.001; pegcetacoplan every other month, −0.69 mm2; 95% CI, −0.98 to −0.39; P < 0.001).

They also mentioned that this association was more pronounced with more frequent dosing (pegcetacoplan monthly vs. pegcetacoplan every other month at month 24, −0.17 mm2; 95% CI, −0.43 to 0.08; P = 0.17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month, the authors reported.

“These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors,” Dr Fu and associates concluded.

References

1. Fu DJ, Bagga P, Naik G, et al. Pegcetacoplan treatment and consensus features of geographic atrophy over 24 months. JAMA Ophthalmol. Published online May 9, 2024. doi:10.1001/jamaophthalmol.2024.1269

2. Arslan J, Samarasinghe G, Benke KK, et al. Artificial intelligence algorithms for analysis of geographic atrophy: a review and evaluation. Transl Vis Sci Technol. 2020;9:57. doi:10.1167/tvst.9.2.57

3. Cleland SC, Konda SM, Danis RP, et al. Quantification of geographic atrophy using spectral domain OCT in age-related macular degeneration.Ophthalmol Retina. 2021;5:41-48. doi:10.1016/j.oret.2020.07.006

4. Wu Z, Schmitz-Valckenberg S, Blodi BA, et al. Reticular pseudodrusen: interreader agreement of evaluation on OCT imaging in age-related macular degeneration.Ophthalmol Sci. 2023;3(4):100325. doi:10.1016/j.xops.2023.100325