Ophthalmology · Clinical trials
Geographic Atrophy Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About geographic atrophy — and why its trials are hard
Geographic atrophy (GA) is an advanced, irreversible form of dry age-related macular degeneration characterized by expanding regions of retinal pigment epithelium and photoreceptor loss, producing scotomas and progressive central vision decline. For decades no therapy existed. The complement cascade's role in AMD drove development of intravitreal complement inhibitors, and in 2023 the FDA approved the first two GA drugs: pegcetacoplan (Syfovre), a C3 inhibitor, and avacincaptad pegol (Izervay), a C5 inhibitor. Both slow the anatomic growth of GA lesions on fundus autofluorescence and OCT. A crucial caveat frames the field: these agents demonstrably reduce lesion enlargement but have not shown a proven, clinically meaningful benefit for patient-reported vision or standard visual acuity, and both carry risks including intraocular inflammation and increased incidence of neovascular AMD conversion. Treatment requires ongoing monthly or every-other-month injections. Endpoint interpretation (anatomy versus function) remains the central debate in GA therapeutics.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Pegcetacoplan (Syfovre) | 2023 | Intravitreal C3 complement inhibitor for GA secondary to AMD; monthly or every-other-month | OAKS and DERBY (phase 3, Lancet 2023) | Change in total GA lesion area on fundus autofluorescence at 12 months (primary); pooled 24-month analyses | OAKS met primary with ~22% (monthly) and ~16% (EOM) reduction in GA growth vs sham at 12 months; DERBY missed at 12 months but pooled/24-month data showed significant slowing (up to ~18-22%). No proven visual function benefit. |
| Avacincaptad pegol (Izervay) | 2023 | Intravitreal C5 complement inhibitor for GA secondary to AMD; monthly | GATHER1 and GATHER2 (phase 3; GATHER2 Lancet 2023) | Mean rate of change in GA area (square-root transformed) over 12 months | ~27% reduction in GA growth rate at 12 months in GATHER1 and ~14-18% in GATHER2 vs sham; anatomic slowing without a proven visual acuity benefit. |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in geographic atrophy development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Lampalizumab (anti-factor D) — CHROMA and SPECTRI (phase 3, Genentech) | Failed to reduce GA lesion enlargement versus sham; primary anatomic endpoint not met, program discontinued | Factor D inhibition insufficient to alter complement-driven GA progression at the retina; possible target/dose limitations. |
Choosing the right endpoint
Primary endpoints that matter in geographic atrophy trials
- GA lesion area growth (fundus autofluorescence) — Primary regulatory endpoint; measures anatomic slowing of atrophy expansion, not vision.
- Square-root transformed GA growth rate — Adjusts for dependence of growth on baseline lesion size, improving statistical sensitivity.
- Best-corrected visual acuity (BCVA) — Functional measure; neither approved drug has shown a robust, proven BCVA benefit.
- Low-luminance visual acuity / reading speed — Exploratory functional endpoints reflecting real-world visual disability in GA.
How iNGENū runs geographic atrophy trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Geographic Atrophy clinical trials — FAQs
Do Syfovre and Izervay restore or improve vision?
How are these drugs given?
What are the main risks?
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