Robyn H. Guymer, Paul Mitchell, James Wong, Jeff Heier, Rishi Singh, Nathan Steinle, David Boyer, Jordie Mones, Giovanni Staurenghi, Frank Holz, Caleb Bliss, Pascal Deschatelets, Federico Grossi, Cedric Francois, Charlie Wykoff, Ramiro Ribeiro

Purpose: Currently, no approved therapies exist to slow the progression of geographic atrophy (GA). Intravitreal pegcetacoplan, a pegylated complement C3 inhibitor pep- tide, demonstrated significant reductions in the growth of GA lesions compared with sham treatment in a pha2 trial. DERBY and OAKS are two 24-month, phase 3, randomised, double-masked, sham-controlled clinical trials comparing the efficacy and safety of monthly or every-other-month intravitreal pegcetacoplan to sham inpatients with GA secondary to age-related macular degeneration

Methods: Enrolled patients are ≥60 years old, have best-corrected visual acuity ≥24 letters, and GA area between
2.5 and 17.5 mm2 or one focal lesion ≥1.25 mm2 if multifocal GA at baseline. The primary endpoint for both studies is change in GA lesion size via fundus autofluorescence from baseline to month 12; secondary endpoints include change from baseline in visual func- tion. Safety measures include incidences of ocular and systemic adverse events.

Results: DERBY and OAKS enrolled N = 621 and N = 638 patients, respectively. Baseline characteristics were well-matched across the groups. Enrolment was completed in June 2020 (DERBY) and July 2020 (OAKS). Twelve-month efficacy and safety data will be presented.

Conclusions: Pegcetacoplan is the only targeted C3 inhibitor being evaluated in phase 3 trials to control lesion growth in GA.