SYFOVRE 5-Year GALE Analysis Shows ~1.5-Year Delay in GA Progression in Nonsubfoveal Disease

Five-year data extend structural benefits but highlight ongoing gaps in functional outcomes

Long-term data in geographic atrophy (GA) is rare, and durable effects are rarer still. A new five-year readout from Apellis offers another look at how complement C3 inhibition performs over time in a disease where structural decline marches on, regardless of therapy. The readout lands at a time when clinicians continue searching for ways to protect sight in a disease that advances even in the best of hands.

What 5 years can reveal

Apellis Pharmaceuticals (Waltham, MA, United States) has released post hoc five-year results from the GALE extension study (n=792), reporting that monthly or every-other-month SYFOVRE (pegcetacoplan injection) delayed GA lesion expansion by about 1.5 years in patients with nonsubfoveal GA.¹

These lesions occur outside the fovea, where slowing atrophy has the greatest chance of preserving usable vision.² The long-term effect, compared against sham or projected sham controls, builds on the structural benefits originally reported in the OAKS and DERBY trials.

GALE followed OAKS and DERBY participants through Month 60. Because sham patients crossed into treatment after Month 24, analysts used a projected sham model to estimate untreated lesion growth from Months 24 to 60, relying on validated linear progression rates.¹

A benefit you can measure, if not always see

After half a decade of follow-up, the pattern is hard to miss. Slowing structural loss over many years is increasingly feasible, yet functional measures such as reading speed, contrast sensitivity and best-corrected visual acuity remain slow to budge.³ GALE microperimetry trends suggest SYFOVRE may help preserve localized retinal sensitivity a bit longer, but translation into daily-life improvements has been subtle.³

“I am very encouraged by these long-term results, which show that early and continuous treatment with SYFOVRE can meaningfully delay the progression of GA,” said Dr. Dilsher Dhoot of California Retina Consultants.¹ “These data indicate that SYFOVRE alters the natural course of this disease, which causes irreversible vision loss and profoundly impacts patients’ daily lives.”

Dr. Caroline Baumal, chief medical officer at Apellis, added that the dataset strengthens the understanding of complement-driven degeneration and the value of targeting C3 over time.¹

Still, the trajectory of GA does not change in its destination. No approved therapy, including SYFOVRE and avacincaptad pegol (Izervay), reverses established damage or halts atrophy entirely.^3,4 The benefit lies in buying time: postponing the moment atrophy reaches the fovea and central vision begins to fade.

Inside the C3 blockade

SYFOVRE is a complement C3 inhibitor aimed at dampening overactivation of the complement cascade, a key driver of retinal cell death in GA.^2,4 In OAKS and DERBY, SYFOVRE reduced lesion growth by 18-22% with monthly dosing and by 17-18% with every-other-month dosing, with stronger effects in nonsubfoveal disease.^1,2 GALE extends that structural narrative by showing that earlier and continuous dosing preserved more retinal tissue over five years than crossover regimens.¹

Five years, modeled controls and careful math

GALE’s five-year nonsubfoveal analysis reports:

Approximately 1.5 years of delayed lesion expansion vs. sham or projected sham¹
Sustained benefit across both dosing intervals¹
No new long-term safety signals¹
Microperimetry trends suggesting slower development of new scotomatous points³

The projected sham is not a conventional control arm but a modeled comparator validated using fellow-eye analyses.¹ The approach helps approximate what untreated atrophy would look like across the full five-year horizon.

What clinicians still watch for

Long-term safety remained consistent with earlier trial phases. Key signals include:

Higher rates of conversion to neovascular AMD with monthly dosing (around 12%), compared with every-other-month dosing (7%) and sham (3%)^2,4
Occasional intraocular inflammation events, including vitritis and anterior chamber cells^1,4
Transient IOP rise after injection, a standard consideration for intravitreal therapy⁴

SYFOVRE does not restore lost vision or cure GA. Its role is to slow the retreat of retinal tissue so patients can hold onto reading, navigation and face recognition for longer.^3-5 In a disease defined by steady erosion, time itself becomes one of the most meaningful currencies.

GA care moves from scarcity to choice

GA has shifted from a therapeutic desert to a steadily diversifying treatment space. SYFOVRE was the first therapy approved for GA, soon followed by avacincaptad pegol (Izervay), which targets complement C5 rather than C3.³ Both agents slow structural progression without reversing existing loss, highlighting the importance of detecting GA early enough for structural preservation to matter.

The growing toolkit is shaping more personalized care. Differences in dosing intervals, safety profiles and disease subtypes are beginning to define treatment selection. Meanwhile, payers and policymakers continue evaluating how structural preservation translates into quality-of-life outcomes for patients already living with irreversible central vision decline.^4-6

Hitting a moving target

GALE suggests that complement inhibition can help shore up retinal real estate while the disease keeps advancing inch by inch. Early, steady treatment seems to buy patients time before the atrophy reaches the fovea, even if it cannot stop the tide completely. Full results are still on the way, though the signals so far echo what earlier studies hinted at.

GA is still a condition without a cure, but the clinical toolbox is expanding. As therapies inch forward, retina specialists may find themselves managing GA less as a sudden cliff and more as a coastline that can, at least for a time, be reinforced against the tide.

Editor’s Note: This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore.

References

Apellis Pharmaceuticals. Apellis announces 5-year GALE data showing SYFOVRE® (pegcetacoplan injection) delayed progression of geographic atrophy by ~1.5 years. Available at: https://investors.apellis.com/news-releases/news-release-details/apellis-announces-5-year-gale-data-showing-syfovrer Accessed on November 14, 2025.
EyeWiki. Pegcetacoplan. Available at: https://eyewiki.org/Pegcetacoplan Accessed on November 14, 2025.
Nissen AHK, Torp TL, Vergmann AS. Clinical outcomes of treatment of geographic atrophy: a narrative review. Ophthalmol Ther. 2025;14(6):1173-1181.
Retina Associates of Western New York. Treatment for geographic atrophy. 2025. Available at: https://retinaassociatesofwny.com/syfovre-treatment-for-geographic-atrophy/ Accessed on November 14, 2025.
Macular Society. Syfovre FAQs and next steps for dry AMD and geographic atrophy treatment. 2025 Feb. Available at: https://www.macularsociety.org/about/media/news/2025/february/syfovre-faqs-and-next-steps-for-dry-amd-and-geographic-atrophy-treatment/ Accessed on November 14, 2025.
SYFOVRE (pegcetacoplan injection) [prescribing information]. Waltham, MA: Apellis Pharmaceuticals, Inc.; July 2025.