Purpose: To report efficacy of intravitreal pegcetacoplan treatment over 36 months in eyes with subfoveal geographic atrophy (GA). Patients and Methods: The GALE (NCT04770545) open-label extension trial adds 12 months of results to the 24-month Phase 3 OAKS (NCT03525613) and DERBY (NCT03525600) trials, representing up to 36 months of continuous pegcetacoplan treatment. They included a heterogeneous population of eyes with subfoveal GA (63%). Pegcetacoplan-treated eyes enrolling in GALE continued at the same interval of pegcetacoplan monthly (PM) or every other month (PEOM). Patients’ eyes in sham monthly or every-other-month arms crossed over to receive pegcetacoplan in GALE at the same interval (sham crossover). Consequently, projected sham, calculated from prior 24-month GA growth rate of sham-observed eyes in OAKS and DERBY averaged across four 6-month segments, was the comparator for the first 12 months of GALE (months 24– 36). This analysis reports results of eyes with subfoveal GA at baseline. Results: In eyes with subfoveal GA, 84% had best corrected visual acuity (BCVA) ≥ 20/200 and 38% had BCVA ≥ 20/63 at OAKS and DERBY baseline. Pegcetacoplan reduced subfoveal GA growth rate by 21% (p< 0.0001) with PM and 19% (p=0.0001) with PEOM over 36 months. Increasing efficacy over time was noted between months 24 and 36; 31% reduction in subfoveal GA growth rate with PM and 25% reduction with PEOM (both p< 0.0001) compared with projected sham. Microperimetry demonstrated significant reduction in formation of absolute scotomas with PM at 24 months (– 2.5 number of scotomas formed; 95% confidence interval CI: – 4.5, – 0.4; p=0.0205) and 36 months (– 4.0 number of scotomas formed; 95% CI: – 6.8, – 1.2; p=0.0050), compared to sham crossover in subfoveal GA. Safety profile in GALE was consistent with OAKS and DERBY. Conclusion: Long-term efficacy of pegcetacoplan in slowing GA progression was demonstrated over 36 months in eyes with subfoveal GA. Plain Language Summary: Why was this study done? Geographic atrophy (GA) is a progressive, permanent retinal degenerative disease that can lead to vision loss in patients over 60 years of age. This analysis was done to look at how pegcetacoplan, a treatment for GA, could help people with GA once it affected the center of their vision, called subfoveal GA. People with subfoveal GA are at risk of losing more of their central vision, which is important for reading, driving, and recognizing faces. What did the researchers do and find? Researchers looked at data from the GALE clinical trial, which followed people with GA for 3 years to see how well pegcetacoplan worked. They studied whether pegcetacoplan slowed down the growth of subfoveal GA and whether it helped lower the risk of forming new blind spots. People with subfoveal GA retained some vision that could be protected. In fact, 84% of them had mild or moderate visual impairment at baseline. Researchers found that pegcetacoplan slowed the growth of subfoveal GA over 3 years, whether it was given every month or every other month. They also found that pegcetacoplan may have lowered the risk of forming new blind spots in the eye. What do these results mean? Pegcetacoplan treatment helped for people with subfoveal GA. Treating subfoveal GA is important because it can help people save the vision they still have and slow down further vision loss. Keywords: pegcetacoplan, complement C3 inhibition, microperimetry, retinal degeneration, clinical trial
Dhoot et al. (Fri,) studied this question.