In this Evidence Based Retina episode, Rishi Singh, MD, FASRS, sits down with Margaret Chang, MD, MS, of Retina Consultants Medical Group in Sacramento, California, to discuss functional outcomes data from the GATHER trials and real-world strategies for introducing complement therapy to geographic atrophy (GA) patients.
IZERVAY fast facts
- IZERVAY (avacincaptad pegol, Astellas Pharma) reduced the risk of progressing to loss of driving eligibility by 41% compared to sham over 24 months in pooled analysis of GATHER1 and GATHER2 trials (12.6% vs 20.1%).1
- Open-label extension study data presented at AAO 2025 demonstrated continued reduction in GA lesion growth for up to 3.5 years with monthly IZERVAY treatment.1
- Earlier intervention with IZERVAY resulted in greater protection of retinal tissue area—disease progression was reduced 37% to 40.5% versus projected sham in the extension study.1
- IZERVAY was well-tolerated with no new safety signals, no cases of retinal vasculitis or occlusive vasculitis, and no increased risk of intraocular inflammation through 3.5 years of treatment.1
- FDA approved an expanded label for IZERVAY in February 2025 without limitation on duration of dosing, providing greater flexibility for long-term GA management.
- More than 210,000 vials of IZERVAY were distributed in the US through December 2024, with month-over-month growth since receiving a permanent J-code in April 2024.
Maintaining mobility: How IZERVAY preserves driving ability
"I think it's really important to absolutely have the patient involved and engaged. A useful way of doing that is to show them their photos and their pictures over time,” explained Dr. Chang. “If they can see that there is an enlargement of geographic atrophy over time, and that it is getting closer to the center of vision, they're much more likely to go ahead with some sort of interventional therapy."
One of the most compelling functional endpoints emerging from the GATHER trials is the impact on driving eligibility—a real-world outcome that resonates deeply with patients facing geographic atrophy. A pooled post-hoc analysis of GATHER1 and GATHER2, presented at ARVO 2026, demonstrated that IZERVAY significantly reduced the risk of progressing to loss of driving.1
"Over 24 months the risk of progressing to loss of driving eligibility was reduced by 41% in patients who received avacincaptad pegol over sham, so that is actually a significant improvement in patient quality of life,” highlighted Dr. Chang.
Further, among patients eligible to drive at baseline (defined as best-corrected visual acuity of ≥70 ETDRS letters), 12.6% of those treated with IZERVAY (monthly or every-other-month) progressed to driving ineligibility (≤60 letters at two consecutive visits) versus 20.1% in the sham group.1 An analysis restricted to monthly-only dosing showed a 35% relative risk reduction (15.1% vs. 20.1%).
Additional functional data on IZERVAY
This functional data adds crucial context to the anatomic benefits demonstrated in the pivotal trials. A 12-month post-hoc analysis published in Ophthalmology Retina found lower proportions of eyes experienced ≥10-letter (11.6% vs. 14.1%), ≥15-letter (4.0% vs 7.6%), or ≥20-letter (1.6% vs 4.5%) BCVA loss with IZERVAY 2mg versus sham.2
The reduction in risk of persistent loss of ≥15 letters (defined as loss at two or more consecutive visits) was particularly notable—3.4% with IZERVAY versus 7.8% with sham through 12 months.2
The long-term extension data presented at AAO 2025 demonstrated that the benefits of IZERVAY continue to accrue over time.3 During the 18-month open-label extension, patients previously treated with IZERVAY monthly or every-other-month in GATHER2 switched to monthly dosing, while former sham patients initiated monthly IZERVAY.
Mean GA lesion growth from months 24 to 42 was reduced 40.5% in patients who received IZERVAY throughout the study versus projected sham.3 Moreover, patients who switched from sham to IZERVAY at month 24 showed 37% reduction in GA growth from months 24 to 42 compared to projected sham—confirming that earlier intervention provides greater cumulative tissue protection.
Safety significance
The safety profile remained consistent through 42 months of follow-up (3.5 years), with no new signals emerging in the extension study.3 Critically, no cases of retinal vasculitis or occlusive vasculitis occurred—a key differentiator from pegcetacoplan (SYFOVRE), the other FDA-approved complement inhibitor for GA.
"This long-term extension study shows increasing efficacy over time, which is very important, but equally impressive is the fact that the safety of IZERVAY was shown to be excellent in long-term follow-up,” noted Dr. Chang. “Safety is especially important when we are treating this condition that doesn’t immediately worsen without treatment."
In February 2025, FDA approved an expanded label based on 2-year GATHER2 data, removing the duration-of-dosing limitation and giving clinicians and patients greater flexibility for chronic disease management.4
In closing
As Dr. Chang emphasizes in her discussion with Dr. Singh, translating anatomic endpoints into functional outcomes patients can understand—like maintaining driving ability—makes the conversation about starting and continuing complement therapy more meaningful.
With cumulative benefit demonstrated through nearly 4 years of follow-up and a reassuring safety profile, IZERVAY offers retina specialists an evidence-based option for slowing GA progression while preserving the activities of daily living that matter most to patients.
For more information on identifying ideal candidates complement therapy, check out: A Guide to Optimal Patient Selection: Enhancing Outcomes in Geographic Atrophy.
