🧠 Study Purpose
- To evaluate the long-term safety and efficacy of pegcetacoplan, the first FDA-approved treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
🧪 Study Design
- GALE is a 36-month, phase 3, open-label extension of the OAKS and DERBY trials.
- Patients continued their original treatment regimens (monthly or every-other-month pegcetacoplan) or switched from sham to active treatment.
👁️ Efficacy Results
- Pegcetacoplan slowed GA progression significantly:
- Monthly dosing (PM-PM): up to 45% reduction in GA growth rate.
- Every-other-month dosing (PEOM-PEOM): up to 33% reduction.
- Greater efficacy observed in nonsubfoveal GA compared to subfoveal GA.
- Treatment effects increased over time, with the most pronounced benefits in the last 6-month interval.
⚠️ Safety Profile
- Over 30 months and ~15,000 injections:
- Exudative AMD occurred in 3.0% of patients in the first 6 months.
- Intraocular inflammation (IOI): 1.3% incidence.
- Ischemic optic neuropathy (ION): 0.1% incidence.
- No cases of infectious endophthalmitis or retinal vasculitis.
- Most adverse events were mild and manageable; serious events were rare.
📊 Statistical Highlights
| Outcome | PM-PM Group | PEOM-PEOM Group | Sham/Projected Sham |
|---|---|---|---|
| GA Growth Reduction (Overall) | 24% | 21% | — |
| GA Growth Reduction (Nonsubfoveal) | 31% | 26% | — |
| GA Growth Reduction (Subfoveal) | 21% | 20% | — |
🧬 Clinical Implications
- Pegcetacoplan shows sustained and increasing efficacy over time.
- Offers a favorable safety profile for long-term use.
- Represents a major advancement in GA treatment, especially for nonsubfoveal lesions.
Figure 1 from the GALE study illustrates the mean rate of change in geographic atrophy (GA) area over 30 months across three patient groups:
📊 Overview of Figure 1
The figure is divided into three panels:
- (A) Nonsubfoveal GA
- (B) Subfoveal GA
- (C) Overall GALE population
Each panel compares pegcetacoplan-treated groups (monthly and every-other-month) to sham or projected sham controls using piecewise linear slope analysis with time points at months 6, 12, 18, 24, and 30.
🔍 Key Findings by Panel
(A) Nonsubfoveal GA
- PM-PM group: 31% reduction in GA growth over 30 months.
- PEOM-PEOM group: 26% reduction.
- First 6 months of GALE:
- PM-PM: 45% reduction vs projected sham.
- PEOM-PEOM: 33% reduction.
- Trend: Increasing efficacy over time.
(B) Subfoveal GA
- PM-PM group: 21% reduction over 30 months.
- PEOM-PEOM group: 20% reduction.
- First 6 months of GALE:
- Both groups showed 33% reduction vs projected sham.
- Trend: Modest but consistent benefit.
(C) Overall Population
- PM-PM group: 24% reduction in GA growth.
- PEOM-PEOM group: 21% reduction.
- First 6 months of GALE:
- PM-PM: 39% reduction.
- PEOM-PEOM: 32% reduction.
- Sham crossover group: 14% reduction after switching to pegcetacoplan.
📈 Interpretation
- Pegcetacoplan shows increasing efficacy over time, especially in nonsubfoveal GA.
- The first 6 months of GALE demonstrated stronger treatment effects than the initial 6 months of OAKS/DERBY.
- The projected sham line (dashed) serves as a benchmark, confirming the linear progression of untreated GA.
Goldberg RA, Boyer DS, Holz FG, et al. Pegcetacoplan for geographic atrophy over 30 months: data from OAKS, DERBY, and the GALE long-term extension study. Ophthalmic Surg Lasers Imaging Retina. 2025;56(7):398–406. doi:10.3928/23258160-20250217-01
1. What is the primary purpose of the GALE study involving pegcetacoplan?
✅ The GALE study was designed to evaluate the long-term safety and efficacy of pegcetacoplan, the first FDA-approved treatment for geographic atrophy secondary to age-related macular degeneration.
2. Which dosing regimen showed the highest reduction in GA growth during the first 6 months of the GALE study?
✅ During the first 6 months of the GALE study, the monthly pegcetacoplan group (PM-PM) showed up to a 45% reduction in GA growth, which was the highest among all groups.
3. What was the incidence of intraocular inflammation (IOI) reported in the GALE study?
✅ The GALE study reported a 1.3% incidence of intraocular inflammation (IOI) over 30 months and approximately 15,000 injections.
4. Which type of geographic atrophy showed greater treatment efficacy with pegcetacoplan?
✅ Pegcetacoplan demonstrated greater efficacy in slowing the progression of nonsubfoveal geographic atrophy compared to subfoveal GA.
5. What was the GA growth reduction in the overall population for the PM-PM group over 30 months?
✅ In the overall GALE population, the PM-PM group showed a 24% reduction in GA growth over 30 months.
