Pegcetacoplan slows geographic atrophy growth but carries risk of exudative AMD

For patients with age-related macular degeneration (AMD), intravitreal injections of pegcetacoplan reduce the rate of geographic atrophy (GA) growth but appear to be associated with an unexpected dose-dependent increase in the incidence of new-onset exudative (e)AMD, according to data from the phase II FILLY trial.

Researchers conducted a post hoc analysis of FILLY, which involved 246 patients with AMD-related GA. They were randomized to receive either 15-mg intravitreal pegcetacoplan or sham administered monthly or every other month for 12 months, followed by a 6-month off-treatment period.

Over 18 months, 26 study eyes developed exudation, and the mean time to eAMD diagnosis was 256 days (range, 31–555). Overall, exudation occurred with greater frequency among patients with a baseline history of eAMD in the fellow eye (p=0.016) and a double-layer sign (DLS) on structural Optical coherence tomography (OCT) in the study eye (p=0.0001).

Of 26 study eyes in which eAMD developed, 18 (69 percent) had history of fellow-eye eAMD and 19 (73.1 percent) had DLS at baseline. These numbers were higher than study eyes that did not develop exudation (76 of 217, 35 percent; p=0.0007 and 70 of 215, 32.5 percent; p<0.0001, respectively).

All 21 patients with structural OCT imaging at the time of eAMD diagnosis exhibited subretinal fluid, intraretinal cysts, or both, consistent with exudation. Meanwhile, among 17 patients who underwent fluorescein angiography at eAMD diagnosis, 10 had detectable macular neovascularization, all being occult lesions.

The development of eAMD did not have a meaningful effect on visual acuity, and all patients responded to antivascular endothelial growth factor (VEGF) therapy.

Pegcetacoplan had an acceptable safety profile and will proceed to phase III studies without adjustments to enrolment criteria.