Assessment of geographic atrophy (GA) lesion progression in the phase 3 OAKS and DERBY trials

Abstract

Purpose : To assess the efficacy of pegcetacoplan in patient subgroups based on baseline lesion characteristics and to characterize overall trial results based on treatment response quartiles.

Methods : OAKS (n=637) and DERBY (n=621) are Phase 3, randomized, double-masked, sham-controlled trials. Enrolled patients had BCVA ≥24 letters and GA area of 2.5-17.5 mm². Patients with nonsubfoveal and subfoveal lesions were included. The primary endpoint was change in total area of GA lesions as measured by fundus autofluorescence. Efficacy of pegcetacoplan at 24 months was assessed in patient subgroups based on baseline demographics and GA lesion characteristics. Patients were pooled across trials for this analysis. Subgroups based on age, sex, GA lesion location, focality and laterality, and BCVA were analyzed. Additionally, a quartile analysis based on GA lesion growth (mm²) over 24 months was assessed to further characterize the efficacy of pegcetacoplan. Patients were pooled across trials and trial arms, with Quartile 1 representing slow progressors and Quartile 4, fast progressors. Only patients with Month 24 growth measurements were included.

Results : At Month 24, GA lesion growth across subgroups in the sham arms was in line with natural history studies. Change from baseline in GA lesion growth at Month 24 consistently favored pegcetacoplan vs sham across subgroups including those with nonsubfoveal and subfoveal lesions [(PM=26%, p<0.0001; PEOM=22%, p<0.0001); (PM=19%, p<0.0001; PEOM=16%, p=0.0003), respectively] and those with unifocal and multifocal lesions [(PM=26%, p<0.0001; PEOM=21%, p<0.0007); (PM=20%, p<0.0001; PEOM=17%, p<0.0001), respectively] (Figure 1). In the quartile analysis, Quartile 1 (slow progressors) had a higher proportion of patients from PM and PEOM arms vs sham. Conversely, Quartile 4 (fast progressors) had a higher proportion of sham patients than PM or PEOM.

Conclusions : These analyses demonstrate the consistent efficacy of pegcetacoplan across patient subgroups and with both PM and PEOM dosing. Furthermore, the slowest progressing quartile consisted of a higher proportion of patients treated with pegcetacoplan than sham.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1. LS Mean (95% CI) Treatment Difference at Month 24 in the Change from Baseline in Total Area of GA Lesion(s) (mm²) in the Study Eye by Treatment Group