On this episode of Evidence Based Retina, Rishi Singh, MD, FASRS, and Dilsher Dhoot, MD, FASRS, discuss the 5-year data from the GALE trial and its implications for treating geographic atrophy (GA). Dr. Dhoot is a vitreoretinal specialist at California Retina Consultants and the principal investigator in the GALE trial.
Pegcetacoplan for GA fast facts
- Pegcetacoplan preserved 3.9mm2 of retinal tissue (>1.5 disc area of tissue)1
- Earlier treatment initiation preserved 2x the retinal tissue vs. delayed treatment
- Pegcetacoplan treatment saved ~1.5 years of disease progression
- It had a consistent safety profile compared to OAKS and DERBY1
Deeper dive into GALE
Study design
The GALE trial is a 36-month open-label extension of the phase 3 OAKS and DERBY studies.1 It included patients receiving pegcetacoplan either monthly or every other month, including those from the original sham groups who switched to active treatment.
The study had a high retention rate of approximately 74%, excluding deaths unrelated to treatment.1 Since there was no true sham group in the extension phase, researchers created a "projected sham" model using linear GA growth and fellow-eye data for comparison.
Findings
- Over 5 years, monthly treatment resulted in a 31% reduction in growth rate, while every-other-month treatment showed a 27% reduction in nonsubfoveal GA.1
- For those with subfoveal GA, monthly treatment produced a 21% reduction, and every-other-month treatment produced a 19% reduction.
- There were >1.5 disc areas of retinal tissue preserved over 5 years of pegcetacoplan treatment.
- Earlier treatment initiation preserved twice as much retinal tissue as delayed treatment.
- Pegcetacoplan treatment delayed disease progression by ~1.5 years.
- GALE demonstrated a 67% and 74% retention rate, respectively, when excluding non-treatment-related deaths.1
In discussing the findings, Dr. Dhoot noted, "We saw increasing benefit over time, in the first 24 months of OAKS and DERBY, cumulatively for the entire population, which included non-subfoveal and subfoveal lesions, was 19% and 18%, but in the second 36 months of GALE, those numbers went up to 27% and 26% for monthly and every-other-month, respectively."
Safety
- The most common adverse effects observed in GALE were consistent with those reported in OAKS and DERBY, which included exudative AMD, increased intraocular pressure (IOP), vitreous floaters, conjunctival hemorrhage, cataract, and retinal hemorrhage.1
- There were low rates of endophthalmitis, intraocular inflammation, and ischemic optic neuropathy.
- There were no cases of vasculitis or non-occlusive retinitis during the OAKS, DERBY, or GALE trials, and real-world reports of post-marketing vasculitis have decreased significantly between 2023 and 2025.1
Patient selection and injection protocol
Patient selection is still key when treating GA. Treating patients early, particularly those with non-subfoveal GA, provides the most benefit. For proper injection protocol to mitigate risks such as intraocular inflammation and choroidal neovascularization (CNV), it is best to dose every 7 to 8 weeks, inject in the worst-seeing eye, and avoid bilateral injections on the first visit.
Dr. Dhoot explained, "A lot of times I'll dose (and this is off-label) a little bit less than 0.1, perhaps even 0.07, and the hope is that if there is an inflammatory reaction, it would be less of an inflammatory reaction in that case." The patient subsequently returns in 6 to 8 weeks for reassessment, take a fundus photograph, and an OCT if the patient's responded well.
Given these study results, there is strong interest in the potential launch of a pre-filled syringe to simplify the injection process and potentially reduce endophthalmitis rates.
