Published in Retina

Avacincaptad Pegol for GA: 3-year Results from the GATHER2 Open-Label Extension Trial

Rishi P. Singh, MD, FASRS

Rishi P. Singh, MD, FASRS

Arshad M. Khanani, MD, MA, FASRS

Arshad M. Khanani, MD, MA, FASRS

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In the first episode of Evidence Based Retina, Rishi P. Singh, MD, and Arshad M. Khanani, MD, MA, review data from the GATHER2 open-label extension study.

Welcome to Evidence Based Retina! In this series, Rishi P. Singh, MD, the Chair of Ophthalmology at Mass Eye and Ear Infirmary and Harvard Medical School, keeps retina specialists at the cutting edge of retina care, featuring peer-to-peer conversations with experts on recent findings from clinical trials, exclusive interviews with industry reps, and case reports with fellows.
On the first episode of Evidence Based Retina, Dr. Singh sits down with Arshad M. Khanani, MD, MA, FASRS, a clinical professor at the Reno School of Medicine, University of Nevada and Managing Partner, Director of Clinical Research, and Director of Fellowship at Sierra Eye Associates in Reno, Nevada, to discuss findings from the GATHER2 open-label extension (OLE) study).

GATHER2 OLE fast facts

  • GATHER2 (NCT04435366): A pivotal 2-year study that demonstrated IZERVAY (avacincaptad pegol [ACP] intravitreal solution, Astellas Pharma) slowed geographic atrophy (GA) progression.1
  • OLE (NCT05536297): After 2 years, all patients had the opportunity to enroll in the OLE for an additional 18 months. In total, 278 patients enrolled in OLE, with an 85% completion rate.
  • Design: All patients (receiving sham or ACP) rolled over to the OLE were converted to monthly ACP for 18 months. Efficacy was assessed using a projected sham model and disease progression was measured by mean change in GA lesion growth area (mm2/year).

Findings from the GATHER2 open-label extension trial

Dr. Khanani noted that GATHER2 and the OLE featured unique trial designs, so the data was organized into two subgroups during the analysis:
  • ACP to ACP: Patients who received ACP for 24 months and then an additional 18 months
  • Sham to ACP: Individuals who received sham for 2 years and then ACP for 18 months
Baseline characteristics were well-matched between the subgroups, excluding the baseline GA lesion area, as patients who were treated with ACP for 2 years had reduced GA progression. Consequently, the baseline GA growth (mm2/year) was 11.56mm2/year in the ACP to ACP subgroup and 13.17mm2/year in the sham to ACP subgroup.
Key findings from the GATHER2 OLE include:
  • 2 years of treatment with ACP slowed down GA growth by 17.7% for all patients
  • When including the 18-month data for all patients, the ACP to ACP subgroup had a 28.8% reduction in GA growth lesion compared to sham for 2 years and projected sham for 18 more months
  • The mean change in GA lesion growth was reduced by 40.5% and 37.1% from month 24 compared to predicted sham in the ACP to ACP and sham to ACP subgroups, respectively
  • Protection of retinal tissue area was reported in both subgroups as follows:2
    • ACP to ACP subgroup: 2.92mm2 (1.17 disc areas)
    • Sham to ACP subgroup: 1.83mm2 (0.73 disc areas)
  • Earlier treatment with ACP demonstrated increasing efficacy over time in reduced GFA lesion growth and protection of retinal tissue
Regarding safety, Dr. Khanani pointed out that there were no new safety concerns; however, in line with previous studies, 15% of patients had a transient increase in IOP, and 5 to 9% developed new-onset choroidal neovascularization (CNV). There were no cases of retinal vasculitis or occlusive vasculitis and no increased risk for intraocular inflammation.

Clinical pearl for monitoring GA patients undergoing treatment with complement inhibitors:

Dr. Khanani primarily uses optical coherence tomography (OCT) on a monthly or EOM basis to monitor GA patients for CNV or any other complications and fundus autofluorescence (FAF) every 6 months to track GA lesion growth.

What’s next?

  • For the OLE: Dr. Khanani plans to dig deeper into imaging biomarkers like ellipsoid zone (EZ) changes and responder analyses in patients with foveal and non-foveal GA
  • For GA care: Having a validated AI tool could help with monitoring GA lesion growth, EZ RPE thickness, and other parameters to guide treatment
Quote from Dr. Khanani about measuring visual function endpoints in patients with advanced geographic atrophy next to an image of a microperimeter.

Conclusion

Dr. Khanani explained that he is excited to better understand treatment responses to IZERVAY from this dataset to help himself and colleagues identify the patients who benefit the most from these therapies and determine if measures like low luminance BCVA and EZ at baseline can help guide treatment.
  1. Khanani AM, Danzig CJ, Heier JS, et al. Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 2-year efficacy and safety results from the GATHER2 phase 3 trial. Ophthalmology. Available online December 15, 2025. https://www.aaojournal.org/article/S0161-6420(25)00790-0/fulltext.
  2. Delaney-Gesing A. Real-world data supports IZERVAY’s long-term benefits. Glance by Eyes On Eyecare. October 20, 2025. Accessed December 16, 2025. https://glance.eyesoneyecare.com/stories/2025-10-20/icymi-real-world-data-support-izervay-s-long-term-benefits/.
Rishi P. Singh, MD, FASRS
About Rishi P. Singh, MD, FASRS

Dr. Rishi P. Singh MD is a staff surgeon, vice president, and chief medical officer at the Cleveland Clinic Martin Health and Professor of Ophthalmology at the Lerner College of Medicine in Cleveland Ohio. He received his bachelors and medical degrees from Boston University and completed his residency at the Massachusetts Eye and Infirmary Harvard Combined Program in Boston, Massachusetts. Dr. Singh then completed a medical and surgical fellowship at the Cole Eye Institute in Cleveland,Ohio.

He specializes in the treatment of medical and surgical retinal disease such as diabetic retinopathy, retinal detachment, and age-related macular degeneration. Dr. Singh has authored more than 250 peer reviewed publications, books, and book chapters and serves as the principal investigator of numerous national clinical trials advancing the treatment of retinal disease. Dr. Singh is the former president on the Retina World Congress and is on the board of the American Society of Retina Specialists.

Dr. Singh has been honored with several research recognitions such as the Alpha Omega Alpha Research Award and American Society of Retina Specialists Senior Honor Award.

More by Rishi P. Singh, MD, FASRS
Rishi P. Singh, MD, FASRS
Arshad M. Khanani, MD, MA, FASRS
About Arshad M. Khanani, MD, MA, FASRS

Arshad M. Khanani, MD, MA, FASRS, is a Managing Partner, Director of Clinical Research, and Director of Fellowship at Sierra Eye Associates and Clinical Associate Professor at the University of Nevada, Reno School of Medicine.

Dr. Khanani received a BA and MA in chemistry from Washington University in St. Louis and subsequently pursued a medical degree from Texas Tech University Health Sciences Center, where he also completed his ophthalmology residency. Afterward, he completed a fellowship in vitreoretinal diseases and surgery at the UT Southwestern Medical Center.

Dr. Khanani founded the clinical research department at Sierra Eye Associates, which is now one of the leading clinical research centers in the country. He has served as a principal investigator for over 100 clinical trials and has been a top enroller in the country for multiple phase 1 to 3 trials. In addition, Dr Khanani has been the first one to perform surgical procedures in multiple surgical clinical trials dealing with sustained delivery and gene therapy. He has over 75 scientific publications.

Dr. Khanani also serves as a member of numerous national and international clinical trial steering committees as well as scientific advisory boards with the goal of bringing new treatment options for patients with retinal diseases. Dr. Khanani is frequently invited as a guest speaker at national and international meetings.

Dr. Khanani is an elected member of the Macula Society, Retina Society and has received numerous awards of distinction. In 2019, he received the Nevada Business Magazine Healthcare Heroes Physician of the Year award for his continued dedication to the field of ophthalmology. He has received the Senior Honor Award from the American Society of Retina Specialists (ASRS) and was also awarded the prestigious ASRS Presidents’ Young Investigator Award in 2021.

More by Arshad M. Khanani, MD, MA, FASRS
Arshad M. Khanani, MD, MA, FASRS
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