Long-term efficacy and safety of pegcetacoplan over 36 months including 12-month results of the GALE open-label extension study

Abstract

Purpose : To report the efficacy and safety of long-term intravitreal (IVT) pegcetacoplan treatment in patients with geographic atrophy (GA) over 36 months.

Methods : The pivotal phase 3 OAKS and DERBY studies evaluated IVT pegcetacoplan treatment for GA secondary to age-related macular degeneration over 24 months. Both subfoveal and nonsubfoveal lesions were included and choroidal neovascularization in the fellow eye was non-exclusionary. Eyes were randomized 2:2:1:1 to pegcetacoplan monthly (PM), pegcetacoplan every other month (PEOM), sham monthly, or sham every other month. After completion of OAKS and DERBY, participants had the option to enroll in the GALE 3-year open-label extension study. Patients in pegcetacoplan arms in OAKS and DERBY continued the same treatment regimen, and patients on sham were switched to pegcetacoplan at the same interval.

Results : In OAKS and DERBY pooled (n=1258) from baseline to Month 24, pegcetacoplan reduced GA lesion growth vs sham across all lesion subtypes by 21% with PM and 17% with PEOM (both p<0.0001; nominal). In eyes with nonsubfoveal GA (n=446), pegcetacoplan reduced GA lesion growth by 26% with PM and 22% with PEOM (both p<0.0001; nominal). In eyes with subfoveal GA (n=765), pegcetacoplan reduced GA growth by 19% with PM (p<0.0001; nominal) and 16% with PEOM (p<0.0003; nominal). Regarding visual function, severe visual impairment (defined as BCVA ≤35 ETDRS letters sustained for ≥4 months without later recovery to ≥40 letters) occurred in 6.4%, 9.6% and 12.0% of PM, PEOM and sham (pooled), respectively, by Month 24, corresponding to 38% (PM) and 12% (PEOM) reduced risk of progression to severe visual impairment. Overall, 83% (n=782) of patients who completed OAKS and DERBY entered GALE, and 92% (n=727) enrolled in GALE completed the first 12 months. Between Months 24 and 36, pegcetacoplan reduced GA growth vs projected sham by 35% with PM and 24% with PEOM (both p<0.0001; nominal): in nonsubfoveal GA by 42% with PM and 28% with PEOM, and in subfoveal GA by 31% with PM and 25% with PEOM. Sham patients from OAKS and DERBY who initiated pegcetacoplan in GALE had a 19% reduction in GA growth vs projected sham at 12 months. The safety profile in the first 12 months of GALE was consistent with OAKS and DERBY with no new safety signals.

Conclusions : Long-term efficacy and safety of IVT pegcetacoplan were demonstrated in patients with GA.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.