This transcript has been edited for clarity.

Hi everyone, I’m Dilsher S. Dhoot, MD, with California Retina Consultants, and I had the pleasure of presenting 5-year data on pegcetacoplan (Syfovre; Apellis Pharmaceuticals) treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) at the 49th annual meeting of the Macula Society in Coronado, California.

By way of review, OAKS, DERBY, and GALE are the largest open-label extension and longest clinical programs in GA. Patients with GA secondary to AMD were randomized in a 2:2 and 1:1 fashion to pegcetacoplan monthly, pegcetacoplan every other month, or sham monthly or sham every other month for OAKS and DERBY.

The OAKS and DERBY pivotal phase 3 trials continued for 24 months, after which patients were eligible to cross over into GALE, the open-label extension trial, which ran for an additional 36 months for a total of 5 years of continuous pegcetacoplan treatment. Those patients on pegcetacoplan continued on the same regimen. Sham patients crossed over to active treatment at the same interval. Efficacy endpoints included growth of the GA lesion, and safety endpoints were also evaluated.

The disposition of GALE at 36 months was fantastic. Sixty-seven percent of patients were retained, and considering that this is an elderly population and during COVID, if we exclude deaths not related to pegcetacoplan, we saw 74% in GALE. It’s important to keep in mind that the sham patients at the end of 24 months all crossed over into active treatment. Therefore, we don’t have a true sham from months 24 to 60, but we have a projected sham. The projected sham methodology is statistically rigorous in GALE and developed via a literature-based approach from Janet Sunness’s work on predicting GA lesion growth.¹ Based on the assumption that GA lesions grow in a linear fashion and validated through a fellow eye analysis. In fact, the fellow eyes grew at a rate of 1.92 mm², which is almost identical to the average annual mean slope in the projected sham, 1.98 mm².

Looking at this population, in OAKS and DERBY months 0 to 24, the reduction in GA growth in the monthly and every-other-month groups was 19% and 18%. In the subsequent 36 months of GALE, we saw a 27% and 26% reduction in growth in the monthly and every-other-month groups. Overall, we saw a 24% and 23% reduction across the entire population, including both nonsubfoveal and subfoveal patients. Focusing just on the nonsubfoveal patients, the first 24 months showed a 27% and 24% reduction, and in the subsequent 36 months, a 33% and 30% reduction. Overall, that’s a 31% and 27% reduction in the monthly and every-other-month groups compared to the projected sham.

Ultimately, we are saving retinal tissue. Through 5 years, this benefit increases year over year—from 0.7 mm² the first year up to 3.9 mm² of preserved tissue by the fifth year. This is over 1.5 disc areas saved over time. Early pegcetacoplan treatment also led to a greater amount of tissue preserved. Patients treated continuously for 5 continuous years preserved 3.9 mm², while those who crossed over from the sham group at month 24 preserved 1.9 mm²—a twofold difference.

Finally, another benefit that certainly resonated with patients is that treatment saved approximately one and a half years of disease progression by 60 months. Tissue preservation is seen as early as the first year, around 3 months saved, increasing each year up to 60 months.

In terms of safety profile, GALE remained consistent with OAKS and DERBY. The rate of infectious endophthalmitis was 0.04%, intraocular inflammation 0.24%, with all cases mild or moderate; those cases that required treatment were managed with topical medications. The rate of ischemic optic neuropathy was 0.02%, and there were no study events of occlusive or nonocclusive retinitis or vasculitis.

To summarize the GALE 5-year data: we see pegcetacoplan preserved 3.9 mm² of retinal tissue, just over 1.5 disc areas; earlier treatment initiation preserved 2 times the retinal tissue vs delayed treatment; approximately one and a half years of disease progression were saved, which resonates with patients; and, finally and most importantly, we see a consistent safety profile with no new signals observed.

Thank you all for listening. RP

Dilsher S. Dhoot, MD, a vitreoretinal surgeon and clinical trial investigator, is a partner at California Retina Consultants in Santa Barbara, California. He is a consultant to Apellis Pharmaceuticals, and the study discussed here was funded by Apellis.

References

1. Sunness JS, Margalit E, Srikumaran D, et al. The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology. 2007;114(2):271-277. doi:10.1016/j.ophtha.2006.09.016