Avacincaptad pegol analysis links GA treatment to preserved driving vision

A pooled post hoc analysis of the phase 3 GATHER1 (NCT02686658) and GATHER2 (NCT04435366) programs suggests that avacincaptad pegol intravitreal solution (Izervay; Astellas) may reduce the risk of losing visual acuity thresholds associated with driving eligibility in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD), according to data presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting in Denver, Colorado, from May 4-7, 2026.¹ The finding introduces a functional measure to a treatment class that has largely been evaluated on anatomic slowing of GA enlargement rather than patient-centered outcomes.

“Geographic atrophy is a progressive disease associated with vision loss that can affect many aspects of daily life, including the ability to drive,” Margaret Chang, MD, MS, of Retinal Consultants Medical Group, Sacramento, California, said in a statement.¹ “Findings from this study suggest Izervay slows GA progression, which could allow some patients to continue to do the things they love for longer.”

Investigators evaluated patients from GATHER1 and GATHER2 who were considered eligible to drive at baseline, defined as best-corrected visual acuity (BCVA) of at least 70 Early Treatment Diabetic Retinopathy Study letters in the study eye. The control group received a sham procedure, in which a needle was applied to the eye without injection. Among 403 such patients, baseline BCVA was similar in the avacincaptad pegol and sham groups (76.2 vs 76.0 letters). Loss of driving eligibility was defined as BCVA of 60 letters or fewer at 2 consecutive postbaseline visits over 24 months.¹

According to the company, the cumulative risk of progressing to loss of driving eligibility at month 24 was 12.6% in patients treated monthly or every other month with avacincaptad pegol vs 20.1% with sham, a relative risk reduction of 41% (nominal P = .0594). In an analysis restricted to monthly dosing vs sham, the risk was 15.1% vs 20.1%, corresponding to a 35% relative risk reduction (nominal P = .1584). The company stated that similar findings were observed among patients who switched from monthly to every-other-month dosing in GATHER2 year 2.¹

“Anytime we are doing a post-hoc analysis, especially with smaller numbers, it is reasonable to be cautious about drawing definitive conclusions. However, the signal and trend are consistent with previous statistically significant analyses of the GATHER data, and help support the evidence that treatment of patients with GA slows the rate of GA progression.”
—Margaret Chang, MD, MS

Reading the Data: A Meaningful Signal With Important Caveats

Those results should be interpreted cautiously. The analysis was post hoc and exploratory, and the nominal P values did not meet conventional thresholds for statistical significance.¹ Driving eligibility itself also varies by jurisdiction and typically depends on binocular function and other visual parameters, not only BCVA in the study eye. Chang said to Ophthalmology Times that it may be more difficult for monocular patients to accurately judge depth of field, particularly at night, and that she generally counsels monocular patients to avoid night driving and to take extra care in unfamiliar areas—though many learn to adapt and drive safely. She added that patients with macular degeneration who have lost central vision often retain intact peripheral vision, which can support driving capability.

“Anytime we are doing a post-hoc analysis, especially with smaller numbers, it is reasonable to be cautious about drawing definitive conclusions. However, the signal and trend are consistent with previous statistically significant analyses of the GATHER data, and help support the evidence that treatment of patients with GA slows the rate of GA progression,” Chang said.

The analysis addresses a clinically relevant question in GA, a progressive and irreversible condition for which functional decline often matters more to patients than lesion metrics alone. Complement inhibition has become an important new treatment approach in GA after the US approvals of pegcetacoplan and avacincaptad pegol, both based on slowing of lesion growth rather than demonstrated visual acuity benefit.^2,3 Avacincaptad pegol is a complement C5 inhibitor approved in the US for GA secondary to AMD; in GATHER2, monthly treatment reduced mean GA growth vs sham over 12 months, supporting the regulatory filing.³

The Long-Term Safety Profile and Looking to Future Trials

Astellas also reported encore data from the GATHER2 open-label extension through 3.5 years.¹ Patients originally treated with monthly or every-other-month avacincaptad pegol and then switched to monthly dosing in the extension had a 40.5% reduction in mean change in GA lesion growth area from months 24 to 42 vs projected sham, whereas patients initially assigned to sham and later switched to monthly active treatment had a 37.0% reduction vs projected sham (P <.001 for each), according to the presentation. The company said the extension showed no new safety signals, no cases of retinal vasculitis or occlusive vasculitis, and no increased risk of intraocular inflammation.¹

That longer-term safety framing is relevant because intravitreal complement inhibition has raised class-wide questions about inflammation and conversion to exudative AMD. FDA labeling for avacincaptad pegol includes warnings regarding endophthalmitis, retinal detachment, transient increases in intraocular pressure, and neovascular AMD.² In the pivotal literature, macular neovascularization occurred more often with active treatment than with sham.³

Binocular visual function was not measured as part of the GATHER trials, though Chang said to Ophthalmology Times that incorporating such measures in future trials would be worth considering as interest in functional outcomes grows. Many prospective trials are already examining secondary functional outcomes including low luminance visual acuity, contrast sensitivity, and reading speed. "Driving simulation would certainly be a reasonable consideration," Chang said.

References

1. Astellas Pharma US, Inc. IZERVAY® (avacincaptad pegol intravitreal solution) demonstrated increased probability of maintaining driving eligibility in geographic atrophy patients. News release. May 12, 2026. Accessed May 12, 2026. https://www.prnewswire.com/news-releases/izervay-avacincaptad-pegol-intravitreal-solution-demonstrated-increased-probability-of-maintaining-driving-eligibility-in-geographic-atrophy-patients-302768710.html
2. US Food and Drug Administration. IZERVAY (avacincaptad pegol intravitreal solution) prescribing information. Accessed May 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217225s001lbl.pdf
3. Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: a randomized pivotal phase 3 trial. Ophthalmology. 2023;130(11):1178-1188. doi:10.1016/j.ophtha.2023.06.024