Apellis Pharmaceuticals, Inc. announced top-line data at 24 months showing increased effects over time with intravitreal pegcetacoplan, an investigational, targeted C3 therapy, in the Phase 3 DERBY and OAKS studies in geographic atrophy (GA) secondary to age-related macular degeneration (AMD). “I am thrilled to see the increased effects over time, which suggest that pegcetacoplan is preserving more and more photoreceptor cells that are directly responsible for vision,” said Eleonora Lad, M.D., Ph.D., lead principal investigator for the OAKS study, associate professor of ophthalmology, director of ophthalmology clinical research unit, Duke University Medical Center. “The vision loss caused by GA is devastating for patients, taking away their ability to perform critical daily tasks like driving, reading, and recognizing faces.

It is very exciting to finally be on the brink of the first potential GA treatment with pegcetacoplan.” In a pre-specified analysis of GA lesion growth over 24 months, both monthly and every-other-month (EOM) pegcetacoplan showed a clinically meaningful reduction in GA lesion growth from baseline compared to sham (all p-values are nominal): DERBY: 19% monthly, p=0.0004; 16% EOM, p=0.0030 OAKS: 22% monthly, p<0.0001; 18% EOM, p=0.0002 Between months 18-24, the pegcetacoplan treatment effect accelerated compared to previous six-month periods, with robust reductions of GA lesion growth versus sham (all p-values are nominal). The increased effects were driven by a greater slowing of lesion growth by pegcetacoplan and not by an increase in the lesion growth rate in the sham group, which was highly consistent over each of the four six-month intervals (1.0+/-0.05 mm2). DERBY: 36% monthly, p<0.0001; 29% EOM, p=0.0002 OAKS: 24% monthly, p=0.0080; 25% EOM, p=0.0007 Additionally, the reduction of GA lesion growth in patients with extrafoveal lesions (28% monthly; 28% EOM) was comparable to the reduction in patients with foveal lesions (34% monthly; 28% EOM) in the combined studies between months 18-24.

Consistent with expectations, no clinically meaningful difference was observed between pegcetacoplan and sham in the key secondary endpoints measuring visual function at 24 months. Studies show that GA lesion growth is correlated with loss of visual function over longer periods of time.1 The visual function outcomes at 24 months are believed to be due to the limitations of the endpoints when used for GA and the relatively early assessment timeframe. Patients will be treated with pegcetacoplan in the GALE extension study for an additional three years.