Geographic Atrophy Treatment in Australia: New TGA-Approved Therapies for Dry AMD

Geographic atrophy (GA) is the advanced form of dry age-related macular degeneration (AMD) and has historically been one of the most challenging conditions in ophthalmology because no treatment existed to slow its progression. That has changed. Two complement-inhibitor therapies are now TGA-approved in Australia: pegcetacoplan (Syfovre, Apellis Pharmaceuticals), approved in January 2025, and avacincaptad pegol (Izervay, Astellas Pharma), approved in October 2025. Neither is currently PBS-listed, meaning treatment is self-funded, but PBS listing is being actively pursued and may occur in the coming years. This post explains what geographic atrophy is, who is eligible for treatment, what the evidence shows, and what patients and optometrists need to know now.

What is geographic atrophy?

Geographic atrophy is the advanced atrophic form of age-related macular degeneration. It occurs when the retinal pigment epithelium (RPE) and overlying photoreceptors in the macula progressively degenerate and die, leaving areas of atrophy with no remaining visual function. The word "geographic" refers to the map-like appearance of the atrophic lesions on fundus imaging.

GA is distinct from wet (neovascular) AMD, in which abnormal blood vessels grow beneath the retina and cause rapid fluid accumulation and vision loss. GA progresses more slowly than wet AMD but is equally irreversible. The areas of retina destroyed by GA cannot recover. The goal of treatment is to slow the rate at which new areas of retina are lost, thereby preserving vision for longer.

GA affects more than 75,000 Australians and is a leading cause of severe vision loss and legal blindness in people over 60. As the Australian population ages, the prevalence of GA is expected to increase substantially over the coming decades.

How does geographic atrophy progress?

GA begins as small areas of atrophy outside the fovea (the central point of the macula responsible for the sharpest vision) and expands over time. Early non-central GA may cause minimal visual symptoms, making detection at routine eye examination critical. As lesions expand toward and eventually involve the fovea, central vision deteriorates progressively. Patients may notice difficulty reading, recognising faces, seeing fine detail, and adapting to changes in lighting.

The rate of GA progression varies significantly between individuals. Average lesion growth rates in clinical trials have been approximately 1.5 to 2.5 mm² per year, but individual variation is wide. Certain OCT biomarkers including incomplete and complete RPE and outer retinal atrophy (iRORA and cRORA), hyperreflective foci, choroidal hypertransmission, and ellipsoid zone loss predict faster progression and inform decisions about monitoring frequency and treatment candidacy.

The complement system and why it is the treatment target

Both TGA-approved treatments for GA work by inhibiting the complement system, a branch of the immune system that has been implicated in AMD pathogenesis for over two decades. Genetic studies have consistently identified complement pathway genes, particularly complement factor H (CFH), complement factor B, and complement component 3 (C3), as major risk factors for AMD. In GA, dysregulated complement activation is thought to drive chronic inflammation that progressively damages the RPE and photoreceptors.

Pegcetacoplan (Syfovre) inhibits complement C3, the central convergence point of all three complement activation pathways (classical, lectin, and alternative), providing broad complement suppression. Avacincaptad pegol (Izervay) inhibits complement C5, a downstream component of the complement cascade. The different targets within the same pathway mean the two drugs have somewhat different mechanisms and potentially different safety and efficacy profiles, though direct head-to-head comparison trials have not been conducted.

Pegcetacoplan (Syfovre): evidence and TGA approval

Pegcetacoplan received TGA approval on 27 January 2025, making Australia the first country outside the United States to approve a treatment for geographic atrophy. The approval was based on results from two Phase 3 trials, OAKS and DERBY, published in The Lancet in October 2023.

OAKS and DERBY enrolled 1,258 patients aged 60 and over with GA secondary to AMD across 232 clinical sites worldwide. Patients were randomised to intravitreal pegcetacoplan monthly, every other month, or sham injection. The primary endpoint was change in GA lesion area by fundus autofluorescence at 12 months.

In OAKS, pegcetacoplan monthly slowed GA lesion growth by 21% and every-other-month dosing slowed lesion growth by 16% compared with sham at 12 months (Heier et al., Lancet 2023). Results from the DERBY trial showed a trend in the same direction though the every-other-month arm did not reach statistical significance at 12 months. Pooled 24-month data from both trials showed increasing effect size over time.

The GALE open-label extension study has reported data through 36 months, showing continued and increasing benefit with longer treatment duration. At 36 months, pegcetacoplan demonstrated up to 38% reduction in the risk of persistent severe visual impairment (American Journal of Ophthalmology 2025).

The TGA-approved indication for pegcetacoplan is every-other-month intravitreal injection for adult patients with GA secondary to AMD with an intact fovea and when central vision is threatened by GA lesion growth.

An important safety consideration is the risk of conversion from dry to wet (neovascular) AMD in patients treated with pegcetacoplan. In the OAKS and DERBY trials, the rate of new-onset neovascular AMD was higher in the pegcetacoplan arms than in the sham arms. Patients on this treatment require regular OCT monitoring for signs of neovascular conversion, and anti-VEGF therapy can be administered concurrently if conversion occurs.

Avacincaptad pegol (Izervay): evidence and TGA approval

Avacincaptad pegol received TGA registration on 13 October 2025, becoming the second treatment for geographic atrophy approved in Australia. The approval was based on the GATHER1 and GATHER2 phase 3 trials, also published in The Lancet in October 2023.

GATHER2 enrolled 448 patients randomised 1:1 to monthly avacincaptad pegol 2mg or sham. At 12 months, avacincaptad pegol significantly slowed GA lesion growth by 18% compared with sham (Khanani et al., Lancet 2023). The GATHER1 trial (phase 2/3) demonstrated a 35% reduction in GA lesion growth over 12 months. Two-year results from GATHER2 showed sustained efficacy, with clinical benefit observed as early as six months from the first injection.

The TGA-approved indication mirrors that of pegcetacoplan: monthly intravitreal injection for adult patients with GA secondary to AMD with an intact fovea and when central vision is threatened by GA lesion growth.

The safety profile of avacincaptad pegol in the GATHER trials was generally favourable. Avacincaptad pegol also carries a risk of neovascular AMD conversion, though the rate in GATHER2 was lower than that reported in the pegcetacoplan trials. As with pegcetacoplan, regular OCT monitoring is required.

Comparing the two treatments

No head-to-head trials comparing pegcetacoplan and avacincaptad pegol have been conducted. The two drugs cannot be directly compared on the basis of their respective trial results because of differences in trial design, patient populations, and primary endpoint methodology.

The key differences are: pegcetacoplan targets C3 (broader complement inhibition) and is approved for every-other-month dosing; avacincaptad pegol targets C5 (more distal inhibition) and is approved for monthly dosing. Both are delivered as intravitreal injections in the same manner as anti-VEGF therapy for wet AMD. Both are indicated only for patients with an intact fovea and threatened central vision. Neither is currently PBS-listed.

The choice between agents, where both are available, will be guided by individual patient factors, clinical experience, and ongoing real-world evidence as it accumulates.

The structural-functional paradox

One of the most important concepts in counselling patients about GA treatment is the structural-functional paradox. Both approved therapies demonstrate statistically significant slowing of GA lesion growth on structural imaging (fundus autofluorescence and OCT). However, neither trial demonstrated a statistically significant benefit on standard measures of visual acuity (ETDRS letter score) within the trial follow-up periods.

This does not mean the treatments do not work. GA lesion growth is a validated surrogate endpoint accepted by the TGA and FDA as a basis for approval. Slowing lesion growth means preserving more retinal tissue, which over time should translate to better preservation of functional vision than would otherwise occur. The GALE extension data showing reduced risk of persistent severe visual impairment at 36 months supports this interpretation. However, patients need to understand that treatment will not restore lost vision and may not produce a measurable improvement in their measured visual acuity in the short term. The benefit is in slowing the trajectory of further loss.

Who is eligible for treatment?

The TGA-approved indication for both agents is: adult patients with geographic atrophy secondary to AMD with an intact fovea and when central vision is threatened by GA lesion growth.

In practical terms, eligible patients are those with confirmed GA on multimodal imaging (fundus autofluorescence and OCT), with lesions that are approaching but have not yet destroyed the fovea, and with evidence that lesion growth is progressing toward the fovea and threatening central vision. Patients whose fovea is already involved and who have already lost central vision from GA are outside the approved indication.

Key eligibility considerations include: confirmation of GA diagnosis by multimodal imaging, assessment of foveal integrity, documentation of lesion growth rate and trajectory, exclusion of active neovascular AMD (anti-VEGF treatment is compatible in patients with prior or concurrent neovascular disease, but active neovascular disease requires separate management), and assessment of patient capacity and willingness to commit to ongoing injection therapy.

In patients with coexisting cataract and GA, the timing of cataract surgery and the initiation of complement-inhibitor therapy requires individual discussion. A cataract can limit fundus visibility and affect the accuracy of GA monitoring; in such cases, addressing the cataract before starting GA treatment may be appropriate.

Given the chronic nature of GA and the monthly or every-other-month injection schedule, treatment involves a significant long-term commitment from both patient and treating clinician. Patient counselling about realistic expectations is an essential part of the treatment decision.

Current access and cost in Australia

Neither pegcetacoplan nor avacincaptad pegol is currently listed on the Pharmaceutical Benefits Scheme (PBS). This means treatment is fully self-funded. The cost of these treatments in Australia is not publicly listed by the manufacturers and varies. Patients interested in accessing treatment should discuss costs with their treating ophthalmologist.

PBS listing is being actively pursued. The Pharmaceutical Benefits Advisory Committee (PBAC) process involves review of cost-effectiveness data and can take considerable time after TGA approval. The timeline for PBS listing is uncertain. When PBS listing occurs, access will expand significantly and costs will reduce substantially for eligible patients.

In the interim, patients who are eligible and motivated to treat may access these therapies as self-funded patients. The decision to proceed requires careful individual discussion weighing the potential benefit of slowed progression against the financial cost and injection burden.

Other evidence-based recommendations for dry AMD and GA

While the new complement-inhibitor therapies are a significant advance, existing evidence-based recommendations for dry AMD remain relevant and should be maintained alongside any new treatment.

AREDS2 supplementation (vitamins C and E, lutein, zeaxanthin, and zinc) has been shown in large randomised trials to reduce the risk of progression from intermediate AMD to advanced AMD (including GA and neovascular AMD) by approximately 25 percent. AREDS2 supplementation is recommended for patients with intermediate AMD or advanced AMD in one eye and should be continued regardless of whether complement-inhibitor therapy is being pursued.

Lifestyle modifications with established evidence include smoking cessation (smoking approximately doubles the risk of AMD progression), UV protection with sunglasses, management of cardiovascular risk factors, and a diet rich in leafy green vegetables and fish. These are not substitutes for treatment but are important adjuncts.

Amsler grid self-monitoring remains important for patients with dry AMD to detect any conversion to wet AMD. New distortion, blurring, or a new blank spot should prompt urgent ophthalmology review rather than waiting for a scheduled appointment.

When should optometrists refer for GA treatment assessment?

Optometrists play a critical role in the early detection and monitoring of AMD, including GA. Referral for GA treatment assessment is appropriate when a patient has confirmed GA on fundus imaging with lesions approaching the fovea, documented progression on serial imaging, and intact foveal function. Earlier referral is preferable to waiting until the fovea is already involved, as treatment is only indicated while the fovea remains intact.

Useful information to include in a referral for GA treatment assessment: current visual acuity, OCT and fundus autofluorescence reports, documentation of GA lesion size and growth on serial imaging, any history of neovascular AMD or prior anti-VEGF treatment, and current AREDS2 supplementation status. For a full guide on what to include in referrals for macular conditions, see the referral information for optometrists and GPs on this site.

For more information on AMD more broadly, including symptoms, the difference between dry and wet AMD, and current treatment options, see the macular degeneration overview at corneaeyedoctor.com.

References

1. Heier JS, Lad EM, Holz FG, et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023;402(10411):1434–1448.
2. Khanani AM, Patel SS, Staurenghi G, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet. 2023;402(10411):1449–1458.
3. Patel SS, Lally DR, Hsu J, et al. Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial. Eye (Lond). 2023;37(17):3551–3557.
4. Apellis Pharmaceuticals. Apellis Receives Approval of SYFOVRE (pegcetacoplan) in Australia for Geographic Atrophy. January 27, 2025.
5. Therapeutic Goods Administration. IZERVAY (avacincaptad pegol). Registered 13 October 2025.
6. Heier JS, et al. Pegcetacoplan Treatment for Geographic Atrophy in Age-Related Macular Degeneration Over 36 Months: Data From OAKS, DERBY, and GALE. American Journal of Ophthalmology. 2025.

Dr Ross MacIntyre BA (Chemistry) MD FRANZCO is a cataract, corneal and refractive surgeon practising in Melbourne. He completed subspecialty fellowship training in cornea, complex cataract and refractive surgery at the Wilmer Eye Institute, Johns Hopkins University, and holds a public appointment at the Royal Victorian Eye and Ear Hospital. He provides intravitreal injection therapy for wet AMD, diabetic macular oedema, and retinal vein occlusion, and can coordinate care for patients with coexisting cataract and macular disease. Consultations are at Northern Eye Consultants, Suite 5, Northpark Hospital Consulting Rooms, 135 Plenty Road, Bundoora. For referrals, call (03) 9466 8822 or use HealthLink EDI nthneyec.