Why Geographic Atrophy Treatments Are Approved in the US but Not Europe: The Endpoint Debate Shaping the Future of Geographic Atrophy Drug Development
Geographic atrophy treatments are approved in the US but not Europe due to differing regulatory perspectives on clinical benefit measurement.
For decades, geographic atrophy represented one of the largest unmet needs in ophthalmology. An advanced form of age-related macular degeneration (AMD), geographic atrophy gradually destroys retinal cells responsible for central vision. Patients lose the ability to read, drive, recognize faces and perform everyday tasks independently. Once that vision is lost, it cannot be restored.
After years of clinical research, the field finally reached an important milestone. The first geographic atrophy treatments gained FDA approval in the US, offering patients an opportunity to slow disease progression. Yet across Europe, the same therapies remain unavailable. The situation highlights a growing challenge in global drug development: What happens when regulators agree on the science behind a disease but disagree on how clinical benefit should be measured?
Learn how our ophthalmology experts help sponsors align endpoint strategy, regulatory expectations and trial execution.
Geographic Atrophy: A Disease Where Preservation May Be the Goal
One of the fundamental realities of geographic atrophy is that it is a neurodegenerative disease. As retinal cells die, lesions expand across the macula. Over time, visual function deteriorates. There are currently multiple molecules and gene therapies under clinical research, and developers are not primarily trying to regenerate damaged tissue or restore lost vision. The current primary objective is to preserve healthy retinal tissue for as long as possible and delay further functional decline. That distinction is important.
In many diseases, efficacy is measured by improvement. In geographic atrophy, the most meaningful outcome may be slowing the rate of deterioration. For patients facing progressive vision loss, preserving function for months or years longer can have a profound impact on their quality of life. The challenge is translating that reality into clinical trial endpoints that satisfy regulators.
The FDA and EMA Are Looking at Different Signals in Geographic Atrophy
The geographic atrophy therapies approved in the US demonstrated an ability to slow the geographic atrophy lesion growth rate within the retina. These structural changes can be measured using advanced retinal imaging and have become widely accepted indicators of disease progression. The logic is straightforward from a development perspective. If geographic atrophy causes retinal lesions to expand and a therapy slows that expansion, the treatment is altering the course of the disease. However, European regulators have taken a more cautious approach.
The EMA has placed greater emphasis on functional outcomes that demonstrate a direct impact on vision. While slowing lesion growth may be biologically meaningful, regulators have questioned whether those structural changes alone are sufficient evidence of a clinical benefit.
This has created a difficult situation for sponsors. Patients treated in clinical trials generally continued to lose vision over time, albeit at a slower rate than untreated patients. The therapies did not restore vision and were not expected to. Their mechanism of action is designed to slow disease progression, not reverse retinal damage. As a result, geographic atrophy drug development now finds itself at the intersection of two valid but competing perspectives: one focused on biological evidence of disease modification and another focused on demonstrable functional improvement.
What This Means for Ophthalmology Drug Developers
The implications extend beyond two therapies. Clinical development programs are built around endpoint strategy. Sponsors invest years designing studies, selecting biomarkers and aligning with regulators on how success will be measured. When regulatory expectations diverge across regions, development becomes significantly more complex. For geographic atrophy, that complexity has already influenced commercial and regulatory decisions.
Sponsors have faced difficult questions about whether existing data packages can support approval in multiple markets and whether future studies should be designed differently to satisfy regional requirements. The issue is particularly challenging because geographic atrophy progresses slowly. Demonstrating changes in functional vision often requires longer studies, larger patient populations and significant investment. Meanwhile, patients continue to lose vision.
The Life Sciences Industry Is Already Moving Earlier
Not surprisingly, many developers are shifting their focus upstream. Rather than intervening after geographic atrophy has developed, sponsors are increasingly exploring therapies for earlier stages of AMD. The goal is to prevent or delay progression before irreversible retinal damage occurs.
Scientifically, the approach makes sense. The challenge is that earlier intervention introduces another set of regulatory questions. What endpoints should be used in intermediate AMD? Which biomarkers are sufficiently predictive of long-term outcomes? How much evidence is needed before regulators accept a new measure of disease progression?
The ophthalmology community is actively working to answer these questions, but consensus remains a work in progress.
Geographic Atrophy Is a Preview of a Larger Industry Debate
The discussion surrounding geographic atrophy reflects a broader issue emerging across drug development. As therapies become more targeted and diseases better understood, sponsors increasingly seek to intervene earlier, before irreversible damage occurs. In many cases, the goal is not to restore lost function but to preserve existing function or slow decline. That shift challenges traditional definitions of efficacy. For slowly progressive diseases, waiting for a measurable functional outcome may delay access to therapies that affect underlying disease biology. At the same time, regulators must ensure that patients receive treatments that deliver meaningful clinical value.
Finding the right balance is not easy. Geographic atrophy has become one of the first therapeutic areas where this tension is developing, but it is unlikely to be the last.
Looking Ahead
The future of geographic atrophy drug development will depend not only on new therapies but also on the continued evolution in how clinical benefit is defined and measured.
Novel mechanisms are advancing through the pipeline. Researchers are exploring earlier intervention strategies, new biomarkers and alternative endpoints that may better capture the patient experience. Regulators and industry and academic experts are continuing to evaluate how those measures should be incorporated into future clinical trials.
For now, geographic atrophy serves as a reminder that scientific innovation alone does not determine success in drug development. Progress also depends on a shared understanding of how clinical benefit should be defined and measured. Until that alignment exists, patients in different regions may continue to experience different levels of access to the same innovations.
The future of geographic atrophy drug development will be shaped by more than innovation alone.
Contributors
Head of R&D and Scientific Strategy for Vision
Syneos Health®
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