AAO 2025: Arshad M. Khanani, MD, highlights 3-year results from the GATHER2 open-label extension trial

Arshad M. Khanani, MD, MA, FASRS, of Sierra Eye Associates in Reno, NV, presented new findings from the GATHER2 open-label extension trial, providing the first look at 3-year outcomes with avacincaptad pegol in patients with geographic atrophy (GA).¹ His presentation, delivered during Retina Subspecialty Day at the American Academy of Ophthalmology 2025 annual meeting, October 17–20 in Orlando, FL, builds upon the 2-year GATHER2 study. Khanani shared some of the highlights from the open-label extension trial in an interview with the Eye Care Network.

“The GATHER2 trial was a pivotal study, a 2-year study that showed that avacincaptad pegol slowed down GA growth compared to sham,” Khanani noted. “The primary endpoint was met at 1 year, and of course avacincaptad pegol …is FDA approved for the treatment of geographic atrophy.”

The open-label extension began after completion of GATHER2, allowing all participants regardless of prior treatment assignment to receive avacincaptad pegol monthly for 18 months, he noted. Patients previously on avacincaptad pegol (either monthly or every other month) continued treatment monthly, while those initially randomly assigned to sham crossed over to active therapy, Khanani said. This design allowed investigators to evaluate long-term efficacy, safety, and durability beyond the original 24-month period, he added.

Khanani noted a strong retention rate, with 85% of enrolled patients completing the 18-month extension.¹ “The key findings from this data set,” he explained, “are the efficacy and the safety data from the open-label extension.”

Efficacy was assessed against a projected sham model.¹ Patients who received continuous avacincaptad pegol treatment demonstrated a 40.5% reduction in GA lesion growth compared with projected sham, he said. In participants who switched from sham to avacincaptad pegol, lesion growth was reduced by 37.1%, with benefits evident early and continuing to increase over time, he added. “The bottom line,” Khanani summarized, “is this data set shows that earlier treatment with avacincaptad pegol demonstrated increasing efficacy in slowing GA lesion growth over time.”

Safety findings were consistent with prior data, Khanani noted. “There are no new safety signals that were seen in the open-label extension compared to GATHER2 2-year data set,” he said. “Avacincaptad pegol was well tolerated, and there were no cases of retinal vasculitis or occlusive retinal vasculitis.”

Discussing the clinical implications, Khanani emphasized the importance of early and continuous treatment. “This data set shows that earlier treatment and continuous treatment is better for patients with GA in slowing GA down,” he said. “Starting late will also help slow it down, but starting early is much better than starting late.”

Looking ahead, Khanani noted that real-world evidence continues to reinforce avacincaptad pegol’s safety profile. “Even in the real-world data that has been presented by many of my colleagues to date, we have not seen any new safety signal with avacincaptad pegol, which is very, very reassuring,” he said. He also pointed to ongoing innovation in the GA treatment landscape, including gene therapy, systemic agents, and oral approaches, alongside the currently approved therapies— avacincaptad pegol and pegcetacoplan.

Reflecting on the broader context, Khanani acknowledged the clinical mindset shift required for GA management. “We’re used to seeing a ‘wow’ effect with anti-VEGF drugs,” he said, “but this is very different—this is more like slowing down the worsening.” He reminded colleagues that, although functional gains are difficult to demonstrate in advanced GA, structural preservation remains meaningful. “We are protecting retinal tissue, which all of us know is saving photoreceptor cells,” he added.

REFERENCE

1. Khanani AM. Avacincaptad pegol for GA: 3-year results from the GATHER2 open-label extension trial. Presented at: American Academy of Ophthalmology 2025 annual meeting; October 17-20, 2025; Orlando, FL; Session: RET12.