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Clinical Focus

A look at podium presentations on GA research at ASRS 2025.

ASRS 2025: Geographic atrophy on display

Catch up on recent advancements in retina care, including new therapies for age-related macular degeneration and macular telangiectasia, enhancing patient outcomes.

Navigating the most recent FDA approvals in retina

Q&A: David Eichenbaum, MD, on the ARCHER-2 study for dry AMD and GA

Q&A: Roger A. Goldberg on the 48-Month results from OAKS, DERBY, and GALE open-label extension

Q&A: Jay Chhablani, MD, on the phase 1/2 data for OCU410 from ASRS 2025

Retina specialist Priya Vakharia reveals promising ANX007 trial results, showing potential to prevent vision loss in geographic atrophy with just seven patients treated.

Innovative Treatment Offers Hope for Macular Degeneration

Priya Vakharia, MD, a retina specialist at Retina Vitreous Associates of Florida in Tampa Bay, presented findings from the ARCHER trial investigating geographic atrophy (GA) treatment for dry age-related macular degeneration during the 2025 Retina World Congress annual meeting.

"The ARCHER trial was a phase 2 trial that was looking at the treatment of geographic atrophy, secondary to dry [age-related] macular degeneration," Vakharia said. "In this trial, patients were randomized to either get ANX007 monthly, ANX007 every other month, or sham monthly, or sham every other month. And what I presented today at Rentina World Congress was actually looking at a key secondary endpoint in these patients, which is the 15 letter loss of vision, and doing a number needed to treat analysis, looking to see how many patients you would need to treat in order to prevent 1 case of vision loss. So just to kind of remind the listeners about the trial, the primary endpoint was change in GA lesion growth, which the ARCHER trial did not meet that primary endpoint."

While the trial did not meet its primary endpoint of reducing GA lesion growth, it revealed a significant secondary endpoint: prevention of 15-letter vision loss. The number needed to treat (NNT) analysis showed remarkable potential, with just seven patients treated preventing one case of advanced vision loss.

To contextualize the findings, Vakharia compared the ANX007 NNT of 7 to established therapies like statins (NNT of 125) and aspirin (NNT of 333), highlighting the treatment's promising efficiency. She emphasized the critical importance of early intervention, noting that extrafoveal disease progression rates are higher than foveal involvement.

"I think, first and foremost, I hope we find a treatment for GA that is really effective, not just slowing the rate of growth, but stopping it. I hope that we find a therapy that's really going to change the game for vision, because I think that's what all of us want for our patients and our family members. I hope that's where we're going in the field of ophthalmology. And, you know, I think we can do it. I think we have a lot of great clinical trials, a lot of great research, and it is definitely possible.

Videos

Retina specialist Priya Vakharia, MD, reveals promising ANX007 trial results, showing potential to prevent vision loss in geographic atrophy.

Early intervention helps with vision protection in macular degeneration

Treating Geographic Atrophy in Patients with Concurrent Neovascular AMD

A Retina expert discusses approaches for treating geographic atrophy in patients who also have neovascular AMD, presenting  specific patient cases and providing key insights for successfully managing such cases. 

Video Series

Treating Geographic Atrophy in Patients with Concurrent Neovascular AMD 

Managing a Patient with Bilateral Geographic Atrophy

Carl D. Regillo, MD, FACS, FASRS presents a case study of a  patient with bilateral geographic atrophy, discussing the decision-making process for determining which eye to treat first, considering factors such as the extent of atrophy and vision in each eye. 

Managing a Patient with Bilateral Geographic Atrophy 

FDA-approved Therapies for Geographic Atrophy

An expert retina specialist discusses the recent FDA-approved treatments for geographic atrophy (GA) that slow disease progression and highlights key factors to consider before starting treatment. 

FDA-approved Therapies for Geographic Atrophy 

Geographic Atrophy: Overview, Diagnosis, and Progression

Carl D. Regillo, MD, FACS, FASRS, discusses geographic atrophy, the advanced stage of dry age-related macular degeneration, including its diagnosis, and progression. 

Geographic Atrophy: Overview, Diagnosis, and Progression 

post hoc microperimetry analysis from the OAKS study demonstrating the effectiveness of pegcetacoplan in preserving visual function.

Effectiveness Of Pegcetacoplan In Preserving Visual Function In Geographic Atrophy

This is a video synopsis of a discussion involving Charles C. Wykoff, MD, PhD, where he presents key findings from a study on the long-term utilization of pegcetacoplan (complement C3 inhibitor) in patients with geographic atrophy (GA). The study, named GALE, extends beyond the preceding DERBY and OAKS trials, focusing on the microperimetry data.

Dr. Wykoff emphasizes the significance of microperimetry in understanding visual function from a patient's perspective, particularly in relation to challenges with best-corrected visual acuity and other functional markers. The analysis of microperimetry data reveals a correlation between the preservation of at least one of the four central loci and less vision loss. Patients who lost all four loci during the trial experienced an average loss of 11.7 letters, while those preserving at least one lost only 4.9 letters.

Moreover, a post hoc analysis indicates a 34-36% risk reduction over two years for patients using pegcetacoplan in losing all four central loci. A similar correlation is observed when examining all 16 central macular loci, showing a 43-48% risk reduction in losing these spots over two years with pegcetacoplan.

Dr. Wykoff concludes by highlighting the continued reduction in lesion expansion observed in the GALE study, aligning with the outcomes of DERBY and OAKS trials. Safety signals remain consistent with preceding trials. The GALE study is ongoing, with plans to accumulate three years of data, bringing the total to five years, including continuous pegcetacoplan dosing.

In anticipation of forthcoming data, Dr. Wykoff mentions the phase four trial, GARLAND, an observational study on geographic atrophy involving approximately 300 patients across 30 sites in the United States. This three-year open-label observational study aims to assess real-world safety and efficacy of Pegcetacoplan in GA treatment. The presentation concludes with Dr. Wykoff expressing enthusiasm for sharing more GA treatment data in the months and years to come.

Video synopsis is AI-generated and reviewed by Modern Retina® editorial staff.

Dr Charles Wykoff presents the results of a post hoc microperimetry analysis from the OAKS study demonstrating the effectiveness of pegcetacoplan in preserving visual function.

study design and key findings from the GALE study, an extension of the pivotal phase 3 OAKS and DERBY trials for pegcetacoplan in geographic atrophy.

Efficacy And Safety Of Pegcetacoplan In Geographic Atrophy

This is a video synopsis of a discussion involving Charles C. Wykoff, MD, PhD, where he provides insights into the GALE study, presenting one-year data on the long-term utilization of pegcetacoplan (complement C3 inhibitor) in patients with geographic atrophy (GA). Dr. Wykoff, a retina specialist in Houston, Texas, notes the study's presentation at the American Academy of Ophthalmology in 2023.

The GALE trial serves as a 36-month long-term extension study following the DERBY and OAKS trials, which led to the FDA approval of pegcetacoplan in February 2023 for managing GA. In GALE, patients from DERBY and OAKS were offered the opportunity to continue treatment, creating an open-label extension.

The study design involved three treatment arms: monthly pegcetacoplan, every other month pegcetacoplan, and a sham arm, with patients crossing over to active treatment after completing DERBY and OAKS. Notably, 83% of patients from DERBY and OAKS continued into GALE.

Analyzing the efficacy data, Dr. Wykoff highlights a consistent reduction in GA lesion growth through month 36 with continuous pegcetacoplan treatment. The data shows a 35% reduction with monthly dosing and a 24% reduction with every other month dosing in the last 12 months.

Safety data from GALE aligns with preceding trials, with adverse events including AMD development, intraocular inflammation, ischemic optic neuropathy, and infectious endophthalmitis. The cumulative rate of wet AMD development through three years is about 19.5% with monthly dosing and less than 9% with every other month dosing.

Intraocular inflammation occurred in 0.7% to 3.9% of arms, predominantly mild cases treated with local steroids. Ischemic optic neuropathy and infectious endophthalmitis rates were low, emphasizing the overall safety profile.

Dr. Wykoff concludes by noting the absence of reported cases of vasculitis or retinitis in GALE to date. The synopsis provides a comprehensive overview of the GALE study, emphasizing both efficacy and safety outcomes related to the extended use of pegcetacoplan in GA treatment.

Dr Charles Wykoff discussed the study design and key findings from the GALE study, an extension of the pivotal phase 3 OAKS and DERBY trials for pegcetacoplan in geographic atrophy.

 Hello, my name is Paul Hahn, [MD, PhD], from NJ Retina. Today, I’m going to be presenting my paper from [the] ASRS [American Society of Retina Specialists Annual Meeting] [in Seattle, Washington] in July 2023 titled “Pegcetacoplan vs Avacincaptad Pegol in Patients With Geographic Atrophy: An Anchored Matching-Adjusted Indirect Comparison of the Phase 3 Trials.”

We currently have 2 complement inhibitors for geographic atrophy: pegcetacoplan and avacincaptad pegol. Pegcetacoplan was the first FDA-approved treatment for GA [geographic atrophy], having been approved in February 2023. Avacincaptad pegol was just approved earlier this month [August, 2023], and the slides as shown here are outdated as a result.

Pegcetacoplan and avacincaptad pegol target complement [proteins] but through slightly different mechanisms. Pegcetacoplan works a little further upstream, targeting C3 and C3b, whereas avacincaptad pegol targets C5.

Both have been shown to slow GA growth in [findings from] their pivotal phase 3 trials. Pegcetacoplan was studied in 2 phase 3 trials called OAKS and DERBY, whereas avacincaptad pegol was studied in a single phase 3 trial called GATHER2 [because] the GATHER1 trial was [a] mixed phase 2 and phase 3 study. Pegcetacoplan [was] looked at [in] both nonsubfoveal and subfoveal GA lesions in their clinical trials, with both monthly and every-other-month dosing, whereas avacincaptad pegol was studied in GATHER2 in only nonsubfoveal GA lesions and only with monthly dosing. Interestingly, pegcetacoplan has longer-term data available, demonstrating increasing effects on slowing down geographic atrophy growth over time.

Shown here is a very familiar graph to us. We see a reduction in GA growth in the combined OAKS and DERBY results, focusing only on nonsubfoveal lesions at 12 months, similar to what was [seen] in the avacincaptad pegol study [findings]. If we look at the top-line data here, it may be tempting to compare the raw numbers between the pegcetacoplan and avacincaptad pegol studies to try to get a sense of the relative efficacies. However, we know that this is not the correct approach. It is dangerous and frankly wrong to compare top-line data [such as] this. But there is a better way to do it, and that way is called the anchored matching-adjusted indirect comparison. This is a well-validated methodology used in multiple therapeutic areas and sometimes required by regulatory agencies for approval. In the absence of a head-to-head study, what this approach does is [try] to compare the relative efficacies of [findings from] 2 different studies in 2 different agents, in this case comparing pegcetacoplan vs avacincaptad pegol [in] patients with nonsubfoveal GA secondary to macular degeneration.

In this approach, the first step is to try to apply the inclusion-to-exclusion criteria from the more restrictive trial to the less restrictive trial to match those inclusion-to-exclusion criteria as best as possible. Specific to this, the inclusion-to-exclusion criteria from GATHER2 were applied to individual patient–level data from OAKS and DERBY to select a similar group of patients, including only those with nonsubfoveal GA, excluding those with fellow eye choroidal neovascularization, including a specific range of vision as specified in GATHER2, etc. Once we’ve matched the inclusion-to-exclusion criteria, the next step is to try to balance those 2 populations. And we do this by propensity score weighting to balance key baseline characteristics, which were selected a priori between the 2 trials. And those include things [such as] age, vision, pressure, as well as GA characteristics such as size, laterality, and focality.

After we apply this methodology, we see the sample sizes here. We go from about 320 patients or about 310 patients treated with pegcetacoplan in OAKS and DERBY for nonsubfoveal lesions to about 220 patients after filtering out and matching those criteria. And then we compare the different trial [findings]. Shown here are some of the actual data, and you can see here we compare [findings from] each of the trials, OAKS vs GATHER2, DERBY vs GATHER2, all anchored to a sham arm.

But I’m going to show you this more graphically, which may be easier to see. In this graph, we compare pegcetacoplan monthly to avacincaptad pegol monthly. If we look at the top row, comparing OAKS vs GATHER2 [findings], we see a 37% greater reduction with pegcetacoplan monthly compared with avacincaptad pegol monthly.

And this difference was statistically significant. If we compare DERBY vs GATHER2 results, we see a 12% greater reduction favoring pegcetacoplan monthly, but this difference was not statistically significant. But if we compare both OAKS and DERBY [findings] to GATHER2 [findings], then we find a 30% greater reduction favoring pegcetacoplan monthly, which was significant. If we also look at the pegcetacoplan every-other-month arm and compare that with more frequent dosing with avacincaptad pegol monthly, we find that in each of the comparisons, the numerical results favored pegcetacoplan every other month, but these were not statistically significant.

Of course, there are a lot of limitations to this type of analysis. This is a post hoc analysis of clinical trials. As such, the generalizability to the population and the conclusions need to be interpreted with caution. As a feature of this type of analysis, individual patient–level data were only available for OAKS and DERBY and not for GATHER2, and we therefore had to limit our baseline matching to characteristics that were reported or published for gather2. And other differences may exist in nonobserved characteristics. There were differences in study design and enrollment criteria. The effective sample sizes are reduced by this analysis, but through this analysis, we suggest that pegcetacoplan may have a better efficacy profile than avacincaptad pegol among patients with nonsubfoveal GA. Specifically, if we look at pegcetacoplan monthly, we saw a statistically significant reduction of greater than 30% in GA lesion growth at month 12 for the combined analysis of OAKS and DERBY compared with avacincaptad pegol at the same monthly frequency. One step further, there was no difference in efficacy between every-other-month pegcetacoplan dosing and monthly avacincaptad pegol dosing.

As we now have 2 different drugs [that are] FDA approved for the [management] of geographic atrophy, it’s going to be important for us as clinicians to try to figure out which of these drugs to use. This provides 1 piece of the data, and each of us will have to make our own decision as we start to incorporate these drugs into our armamentarium.

Transcript is AI generated and edited for clarity and readability.

A retina specialist shares his presentation from the 2023 ASRS Annual Meeting, which describes a study comparing the efficacy of 2 FDA-approved treatments for geographic atrophy based on an anchored matching-adjusted indirect comparison of phase 3 trial findings.

Pegcetacoplan vs Avacincaptad Pegol in Patients With Geographic Atrophy

Our team spoke with several researchers and industry professionals at the 2023 American Society of Retina Specialists meeting in Seattle, Washington. We asked them, "What research here do you find exciting or interesting?" Here's what Paul Hahn, MD, Kerrie Brady, BPharm, MBA, MS, and Michael Singer, MD had to say!

- This transcript has been edited for clarity.

You know, one of the best things about these meetings is that you get, you get to learn about different things that are coming. And, you know, we hear about different mechanisms of treatment for geographic atrophy, different mechanisms of treatment for wet AMD, different methods of delivery, gene therapy, and so forth. And, you know, it's really learning more about these at these types of meetings really, what's, what's innovative.

Yes, we're particularly excited about the growth and expansion of AI and machine learning to enable diagnosis. And so with that, with the machines getting smaller, getting more into the community, we are looking forward to being able to detect more patients at earliest stages in their disease. And with a product such as OTT-166, begin early active treatment sooner in their disease process.

I am excited about the possibility and when I looked at patients who were being treated in a high dose Eylea trial, that you're able to get a significant number of patients, 44%, to essentially go 20 or 24 weeks. Even though it's a clinical trial, I think it really potentially has real ramifications to our patients in practice.

We asked, "What research at ASRS 2023 do you find exciting or interesting?" Here's what Paul Hahn, MD, Kerrie Brady, BPharm, MBA, MS, and Michael Singer, MD had to say!

ASRS 2023: Attendees share the topics from the annual meeting that interest them

At the 2023 American Society of Retina Specialists meeting in Seattle, Washington, we asked some of the presenters, "What research here do you find exciting or interesting?" Here's what Diana Do, MD, Shawn Kavoussi, MD, and Durga Borkar, MD, MMCi had to say!

 I think the exciting news in this event was the inflammation associated with some of our newer agents, specifically pegcetacoplan for the treatment of geographic atrophy. It's great that the retina community is working with industry to evaluate these cases of intraocular inflammation and determine the next best steps for our patients.

In general, I'm very excited about new treatment options for a variety of vascular diseases, retinal vascular diseases. It's, we're fortunate to practice in the era we have many options. We can tailor the treatment to the certain patient situation.

I think this is a really exciting and timely meeting in particular given the recent information about safety events for Syforve. I think a lot of the geographic atrophy studies have been particularly interesting and enlightening for me when thinking about how to treat my patients.

Geographic Atrophy

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