New real-world outcomes from an analysis are demonstrating first-ever results regarding SYFOVRE (pegcetacoplan injection) and its benefits for patients with geographic atrophy (GA) and concomitant neovascular (wet) age-related macular degeneration (AMD).
The new data was presented during the American Society of Retina Specialists (ASRS) 2026 annual meeting in Montreal, Canada, this week.
Let’s start with a look at SYFOVRE.
Most importantly: The therapeutic was developed under Apellis Pharmaceuticals and approved by the FDA in 2023 as the first treatment option for patients with GA secondary to age-related macular degeneration (AMD).
What it is: An intravitreally (IVT)-administered formulation dosed once every 25 to 60 days into each affected eye to potentially reduce the progression of GA.
- That dosage: 15 mg/0.1 mL
- See here for its full prescribing information.
Also, check out all our prior coverage on the therapeutic (including post-market clinical data). And take note: Biogen, Inc. recently acquired Apellis and, by extension, SYFOVRE.
And now for this ASRS presentation.
We’ll start the basics of this research:
- The title: Outcomes in Geographic Atrophy: Real-World Evidence from EHR Data and AI-Based Imaging in Patients Treated with Pegcetacoplan
- Its presenter: Nimesh Patel, MD
- His credentials: assistant professor of ophthalmology at Harvard Medical School; vitreoretinal surgeon at Massachusetts Eye and Ear; director of pediatric retina at Mass General Hospital
And the purpose of the analysis: Investigators evaluated the real-world results and treatment patterns associated with pegcetacoplan (SYFOVRE) in clinical practice—particularly in association with its use alongside anti-vascular endothelial growth factor (VEGF) therapies for patients with GA and neovascular (wet) AMD.
Why, exactly?
As Dr. Patel noted, SYFOVRE was approved based on clinical data involving just GA patients, not those with both GA and neovascular (wet) AMD.
Plus, those prior real world studies on SYFOVRE actually found that 25% of patients treated with SYFOVRE also had concurrent wet AMD (but weren’t included in the clinical trials, he added.
So how did they do this?
By conducting a retrospective observational analysis that assessed outcomes among GA patients—both with or without wet AMD—receiving pegcetacoplan.
Critical to this was the utilization of real-world data (RWD) and artificial intelligence (AI)-based imaging.
Tell me more.
Investigators utilized the Vestrum Health Retinal Database, which encompasses electronic health record (EHR) data from U.S. retina specialists.
- The time period for this data: January 2015 to July 2025.
Plus: A separate, independent imaging cohort of 2,000 eyes was also analyzed using the Amaros AI platform, which operates as an ophthalmic answer engine (check out this rundown for more details on how the platform leverages AI).
How were these cohorts set up?
This was a two-arm study in which each arm had a control group, according to Dr. Patel.
- The first cohort: GA and pegcetacoplan-treated GA patients
- Control: patients with GA (but not treated)
- The second cohort: patients with GA + wet AMD treated with pegcetacoplan + anti-VEGF (concomitant therapy)
- Control: patients treated with anti-VEGF alone
Explain how these control groups were matched.
Each was matched to their respective treatment group using a 1:1 propensity score matching based on factors such as:
- GA lesion size
- Distance to the foveal and lesion location
- Age
- Sex
- Visual acuity (VA)
And what was measured from this data?
- VA outcomes among eyes with GA that received ≥1 pegcetacoplan injection
- Index period for this: Feb. 17, 2023 to Jan. 31, 2025
- Dubbed the “pegcetacoplan-treated cohort”
- VA outcomes of eyes not treated with pegcetacoplan
- Dubbed the “untreated controls”
To note: Researchers also analyzed real-world treatment patterns among patients receiving concomitant anti-VEGF therapy.
And the duration of this analysis?
The interim analysis was 18 months.
Importantly: The analysis’s index date was defined as the first pegcetacoplan injection or first visit with GA during the index period.
Next up: baseline numbers.
In the treated cohort:
- Bilateral GA was more common (68.2% vs 46.6%).
- Bilateral VA was also generally better: 55 Early Treatment Diabetic Retinopathy Scale (ETDRS) letters (20/80)
- Compare this to 48 ETDRS letters (20/125) in the untreated cohort
And in the untreated cohort, wet AMD was more common (51.5% vs 31.3%)
How did VA change across both cohorts?
In general: Pegcetacoplan was associated with a slower VA decline versus controls.
We’ll look at the propensity-score-matched cohorts first. For the pegcetacoplan-treated and untreated cohorts, respectively (letters lost; p < 0.05):
- Mean ETDRS at baseline: 57.9 vs 59.9
- Mean ETDRS at 6 months: 57.8 (-0.1) vs 56.2 (-3.7)
- Mean ETDRS at 12 months 54.7 (-3.2) vs 51.2 (-8.7)
By Month 18, the mean ETDRS for each was 52.1 (-5.8) versus 47.0 (-12.9).
And in the second cohort?
To refresh: This consisted of the pegcetacoplan + anti-VEGF-treated patients versus patients treated with only anti-VEGF.
Across all eyes—regardless of VA at index—those change-from-baseline numbers for the treated versus untreated cohorts, respectively, were (p<0.05):
- Mean ETDRS at 6 months: -2.3 vs -1.7
- Mean ETDRS at 12 month:s -4.1 vs -2.9
- Mean ETDRS at 18 months: -6.0 vs -4.0
Translation (for Month 18): While changes were stable (<5 letters lost) for the treated and untreated cohorts, respectively, a mild decline (≥5 and <15 letters lost) was observed at 18 months in both groups.
Next up: Let’s look at patients who lost <15 letters.
Starting with the propensity-score-matched cohorts, with pegcetacoplan-treated-only versus untreated:
- At 6 months: 10.2% vs 16.0% (p = 0.027)
- At 12 month:s 14.5% vs 26.6% (p = 0.003)
- At 18 months: 23.5% vs 28.7% (p = 0.471)
And among that second cohort (pegcetacoplan + anti-VEGF versus anti-VEGF only, respectively):
- At 6 months: 7.9% vs 13.5% (p = 0.027)
- At 12 month:s 11.7% vs 20.9% (p = 0.003)
- At 18 months: 16.0% vs 33.8% (p = 0.471)
The takeaway: Fewer patients lost <15 letters with pegcetacoplan treatment than controls (across the board).
And regarding those other outcome measures?
Foveal-distance change remained minimal over time (-0.19 mm in the combination therapy group), which suggested “limited encroachment,” the authors noted.
Other observations noted:
- Treatment frequency in the treated cohort showed a median of 7 pegcetacoplan injections over 12 months
- Median interval: 57 days
- Anti-VEGF dosing intervals remained stable over time in the concomitant therapy group
- Median interval: 61 days
So, to sum up both analyses’ findings …
Based on this data, the study authors noted that “pegcetacoplan treatment was associated with statistically significant slower VA decline versus the control—both with and without concomitant anti-VEGF therapy.”
- Specifically: Fewer pegcetacoplan-treated patients lost ≥15 ETDRS letters versus control during follow-up, regardless of anti-VEGF use.
For the future: They advise that, while this study was based on real-world data, three additional criteria are needed to confirm these findings: larger sample sizes, longer follow-up, and further statistical adjustment.
And from a big-picture perspective?
In speaking with Glance, Dr Patel shared two noteworthy takeaways:
- This was the first study (real-world or clinical trial) to clearly demonstrate VA benefit for pegcetacoplan in GA, with:
- Slower VA decline vs controls
- Statistically significant reduction in ≥15 (3-line) vision loss in the pegcetacoplan-treated groups
- The study showed real‑world evidence that this benefit extends to GA patients who also have wet AMD.