Efficacy of intravitreal pegcetacoplan in geographic atrophy: 24-month results from the Phase 3 OAKS and DERBY trials
Author Block: Raman Tuli . University of Ottawa.
Author Disclosure Block: R. Tuli: Membership on advisory boards or speakers’ bureaus; Name of for-profit or not-for-profit organization(s); Advisary Board Apellis. Funded grants or Clinical Trials; Name of for-profit or not-for-profit organization(s); Clinical Trial Apellis.
Abstract Title: Efficacy of intravitreal pegcetacoplan in geographic atrophy: 24-month results from the Phase 3 OAKS and DERBY trials
Abstract Body: Purpose: Geographic atrophy (GA) leads to irreversible vision loss and, with no approved treatments available, represents a significant unmet need. Pegcetacoplan, which targets both C3 and C3b in the complement cascade, was studied in a broad GA population in the 24-month OAKS and DERBY Phase 3 trials. Study Design: OAKS and DERBY are two 24-month, Phase 3, randomized, double-masked, sham-controlled Clinical Trials comparing the efficacy and safety of intravitreal pegcetacoplan monthly (PM) or every-other-month (PEOM) with sham injections in patients with GA secondary to age-related macular degeneration. Methods: OAKS (N=637) and DERBY (N=621) enrolled patients aged ≥60 years old who had best-corrected visual acuity ≥24 letters, and GA area 2.5-17.5 mm2, with one focal lesion ≥1.25 mm2 if multifocal GA at baseline. Patients were randomized (2:2:1:1) to receive either intravitreal PM or PEOM or sham treatment (monthly or every other month). The primary endpoint for both studies was change in GA lesion size via fundus autofluorescence imaging from baseline to Month 12 analyzed using a mixed-effects model for repeated measures. Secondary endpoints included change in GA lesion size from baseline to Month 24, best-corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and microperimetry (OAKS only). Results: Pegcetacoplan was associated with a clinically meaningful reduction in GA lesion growth at Month 24 when compared with sham treatment (OAKS: 22% PM, p<0.0001; 18% PEOM, p=0.0002, DERBY:19% PM, p=0.0004; 16% PEOM, p=0.0030). In a combined analysis, an accelerated effect was observed between months 18 and 24 (30% PM, p<0.0001; 24% PEOM, p<0.0001), and treatment effects over 24 months were consistent regardless of lesion location (nonsubfoveal: 26% PM, p<0.0001; 22% PEOM, p<0.0001; subfoveal: 19% PM, p<0.0001; 16% PEOM, p=0.0003). There were no clinically meaningful differences in key functional endpoints observed at 24 months. Microperimetry analyses in the junctional zone of atrophy showed a reduction in the loss of retinal sensitivity (mean threshold sensitivity: PM 0.564 dB higher, p=0.0650; PEOM 0.707 dB higher, p=0.0202) and fewer scotomatous points (PM -0.680 points lower, p=0.1444; PEOM -1.138 points lower; p=0.0140) with pegcetacoplan treatment versus sham over 24 months. Conclusions: Pegcetacoplan slows GA lesion growth with both PM and PEOM dosing, with effects increasing over time. Microperimetry analyses of the junctional zone of GA lesions provided a signal of functional preservation of photoreceptors with pegcetacoplan treatment.
