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This PER On Air - Ophthalmology Times podcast examines the new treatment paradigm for patients with geographic atropy, following the introduction of complement-targeting therapies. In this podcast, experts, Dr Cecelia Koetting and Dr Talia Kaden review some of the key highlights from the live satellite symposium, Community Practice Connection™: Mastering the New Treatment Paradigm in Geographic Atrophy – From Detection to Intervention presented at the 2024 EnVision Summit in Ophthalmology.

Northwell Health and the Manhattan Eye, Ear and Throat Hospital (MEETH)

University of Colorado School of Medicine

This PER On Air - Ophthalmology Times podcast examines the new treatment paradigm for patients with geographic atropy, following the introduction of complement-targeting therapies. 

Mastering the New Treatment Paradigm in Geographic Atrophy – From Detection to Intervention

 EyePod podcast, Mandeep S. Singh, MD, PhD, speaks with Mark S. Humayun, MD, PhD, to learn about the advancements for a novel stem cell patch developed by a team of researchers at USC for the treatment of advanced dry age-related macular degeneration.

Dr. Humayun talks about the inspiration behind the patch, how his expertise in both ophthalmology and biomedical engineering has been crucial, and insights gained from a Phase 1/2a study. Dr. Humayun also outlines the upcoming steps for a multisite Phase 2b clinical trial and envisions the potential future role of the stem cell patch in the treatment of geographic atrophy.

Associate professor of ophthalmology and genetic medicine at the Wilmer Eye Institute at Johns Hopkins University School of Medicine in Baltimore, Maryland

Recipient of the 2023 Andreas C. Dracopoulous Professorship in Ophthalmology

Co-Director of the Genetic Eye Diseases (GEDi) Center and principal investigator at the Center for Stem Cells and Ocular Regenerative Medicine (STORM)

University Professor of Ophthalmology, Keck School of Medicine of USC in Los Angeles, California

Cornelius J. Pings Chair in Biomedical Sciences

Director, USC Ginsberg Institute for Biomedical Therapeutics

Received the National Medal of Technology and Innovation from President Barack Obama in 2016 for his innovative work and development of the Argus II.

In this Ophthalmology Times EyePod podcast, Mandeep S. Singh, MD, PhD, speaks with Mark S. Humayun, MD, PhD, about the progress made by a team of USC researchers on a novel stem cell patch for treating advanced dry age-related macular degeneration.

Innovation Series: A stem cell patch for treating advanced dry AMD

 EyePod podcasts focusing on innovation in ophthalmology. Throughout this series, we'll be hearing insights from various stakeholders including those in clinical practice, academia, and industry. The overarching message in this podcast is intended to be informational and not promotional. Today, our host Ehsan Sadri, MD, engages in a conversation with Jeffry Weinhuff, who is managing partner of Visionary Ventures. And just a quick note: the thoughts and opinions expressed are those of the speakers and do not necessarily represent the opinions of this publication.

 in Newport Beach, California, and is board-certified, fellowship-trained in treating LASIK, cataract, and glaucoma surgeries. He is a co-founder of Visionary Ventures Fund and a consultant to Tarsus.

, a series of venture capital funds which is a leading investor in drugs and devices for the eye. Visionary has current financial interests and serves on board of directors of the following companies: Aurion Biotech; Centricity Vision; CorneaGen; IanTrek; ONL Therapeutics; Orasis Pharmaceuticals; Pelage Pharmaceuticals; Re-Vana Therapeutics; Surface Ophthalmics; Sydnexis; Surface Ophthalmics; TearClear.

Explore cutting-edge ophthalmology innovations in this new series on the Ophthalmology Times EyePod podcast. Throughout this series, we'll hear insights from various stakeholders in clinical practice, academia, and industry. In this episode, host Ehsan Sadri, MD, engages in a conversation with Jeffry Weinhuff, managing partner at Visionary Ventures, exploring trends and offering advice for individuals driven by an entrepreneurial mindset.

(EyePod) From idea to impact: Navigating ophthalmic innovation

Astellas said in a press release that the FDA comments in the CRL relate to proposed labeling language, not safety.

FDA issues CRL to Astellas' Supplemental New Drug Application for avacincaptad pegol intravitreal solution (IZERVAY)

Key findings include reduced lesion growth, retinal tissue preservation, and improved visual function, demonstrating significant potential for the treatment option.

Ocugen announces positive preliminary data from OCU410 Phase 1 clinical trial for geographic atrophy

OCT-based AI analysis brings changes in GA and therapeutic responses into sharp focus.

Shifting the GA paradigm

The investigators undertook a study in which they retrospectively evaluated the presence and amount of small HRF in the eyes of patients with different macular atrophic phenotypes.

Small hyperreflective retinal foci: An in vivo imaging feature of resident microglia activation in geographic atrophy

The agency confirmed its June 2024 negative opinion after Apellis requested re-examination of EMA's initial opinion.

EU CHMP confirms negative opinion on marketing authorization application of intravitreal pegcetacoplan from Apellis

Arshad Khanani, MD, MA FASRS discusses data from GATHER 2 Trial

Sydney M Crago, the editor of Modern Retina, talks with Arshad M Khanani, MD, MA, FASRS, about the expanded efficacy data from the GATHER 2 trial for geographic atrophy (GA).

- This transcript has been edited for clarity.

Hi, I'm Sydney Crago with modern retina and I'm here today with Dr Arshad Khanani to speak about his presentation at the upcoming meeting. He'll be talking about the 2-year expanded efficacy data of the GATHER 2 trial. Dr. Khanani, can you tell us a bit about your presentation?

Thank you, Sydney. So my talk at Angiogenesis 2024 virtual meeting is, is about the expanded efficacy of avacincaptad pegol, or ACP. As you're aware that ACP is a small pegylated RNA aptamer that is designed to be a specific inhibitor of complement C-5. Based on the 2 positive pivotal, GATHER-1 and GATHER-2 studies, ACP received FDA approval in August of last year. In my talk, I'm actually sharing the expanded efficacy data, and there are a few things [that] I wanted to highlight from my presentation. First thing, we know that ACP monthly and every other month reduce GA growth versus sham in GATHER-2. As you recall, gather to is a multicenter, international randomized study where patients receive either monthly ACP in the first year, or sham, and then they were really randomized to receive either monthly or every other month dosing while the sham group continued with the sham injection. 

So, the idea was to see if every other month can result in comparable efficacy as monthly, and that's what we saw. The other thing we notice is the treatment effect, we know that the treatment effect with ACP starts as early as 6 months. And what we saw was the treatment effect, more than doubled at over 2 years, compared to over 1 year with ACP, 2 milligram compared to sham. And then we also looked at the pooled analysis from GATHER-1 and GATHER-2. As you recall, GATHER-1 was a phase 2/3 pivotal study, and it was 18 months. So we wanted to see how pulling the data from GATHER-1 and GATHER-2 in terms of efficacy will give us more information about the treatment effect because we know that the GA is a very variable disease, and it's a multifactorial disease. So what we saw was, we saw robust efficacy of ACP in that analysis, and we saw an almost doubling of treatment effect every 6 months in the 18 months pool analysis with an overall reduction of 19% in GA growth compared to sham. Again, this is a postdoc analysis. And lastly, I presented the first time results of a match-adjusted, indirect comparative analysis or called medac analysis. And these analysis are done when level 1 evidence is missing in a head-to-head study. So we know that pegcetacoplan, which is also another drug that's approved for the treatment of GA. 

That trial enroll patients with central and non-central point involving GA, well, patients in the ACP study, in all, were enrolled with non-centerpoint involvement. So, there are different baseline characteristics of each trial, but what we can do is we can match the baseline BCVA and GA lesion growth across trials and then look at the efficacy. So, we took all the publicly available data for pegcetacoplan DERBY and OAKS study, and then we matched the parameters of bcva GA and other parameters using the data from pivotal GATHER-1 and GATHER-2 studies. And then we ended up with a population that was actually very well matched. And again, this is not level 1 evidence this is done for for payers and regulators, especially when level 1 head-to-head evidence is missing. So what we saw was, we saw greater directional doubling of treatment effect with ACP monthly compared to pegcetacoplan monthly. So I think that is something very informative for the field that if we have similar baseline characteristics, we are comparing the efficacy so we saw a reduction over 12 months of 26% with ACP, in GA growth versus sham, and we use the same in sham from the same study. So we're not comparing the sham from a different study. While we saw a 14% reduction with pegcetacoplan in the similar group. 

So we took all the data from DERBY and OAKS. And then we matched the patients from ACP in this analysis. So this was very important to find that with the match medac analysis, we saw greater benefit with ACP compared to pegcetacoplan. Of course, keeping all the caveats in mind about the limitations. 

And the other thing we looked at which matters most for our patients is vision. So we looked at visual acuity in the sham group, and the match group for ACP. And then we looked at visual acuity in Derby and oaks with every month and every other month. And we saw that ACP monthly demonstrated greater vision preservation verus a sham compared to pegcetacoplan versus sham. So when you look at the data, there is 47% greater preservation of vision compared to share with ACP. And when you look at pegcetacoplan, in the monthly group, there is 17% less vision preservation. And in the every other month group, it's 65% less vision preservation. So this was another interesting finding that patients treated with ACP had greater vision preservation, which is obviously the ultimate goal of treating these patients long term with these therapies. 

So I hope this summary of my talk was helpful to you and thank you for inviting me to share the summary of my talk.

Videos

Angiogenesis 2024: Expanded efficacy data from the GATHER 2 trial for geographic atrophy

CEO of Aviceda shares results from Phase II/III part 1 SIGLEC trail

AAO 2023: SIGLEC Trial Results

Mohammed Genead, MD, CEO of Aviceda spoke with the Ophthalmology Times team about the company's Phase II/III SIGLEC trial part 1 results, which were shared at this year's American Academy of Ophthalmology meeting.

The American Academy of Ophthalmology is holding its annual meeting in San Francisco. During the Eyecelerator event, Aviceda CEO, Mohammed Genead made a presentation on a new patient case study. Thank you for joining us today to tell us about this presentation.

Thanks so much, David, you know, for the opportunity to give more background about our clinical asset AVD-104, but before I will do that, with just quick enough background. We're Aviceda. Aviceda is a private, late clinical-stage biotech company based in Cambridge, US, we have a technology platform called HALOS, High-Affinity Ligands of Siglecs, with a lead asset AVD-104 targeting patients was GA, geographic atrophy secondary to age-related macular degeneration, and also diabetic macular edema. AVD-104, the lead asset, which we're going to give you some key data highlights today about, it's a very promising intravitreal therapy. It's a sialic acid coated nanoparticle was a dual mechanism of action. This acid was designed to modulate the over activation of critical inflammatory celluar and complement pathway, which we knew it's highly implicated in patients was GA, secondary to AMD. And the way the drug works, AVD-104 is inhibiting and repolarizing, the overly activated retina immune cells to the resolution states, as well [as] enhance the activity of complement factor H to regulate the over amplification of the alternative complement cascade.

I would love to highlight about the clinical trial. The clinical trial called SIGLEC. It's a Phase II/III ongoing, US-based clinical trial. The AVD-104 is being going after a patient was GA second to the AMD as well as the diabetic macular edema. The highlight of my presentation at the Eyecelerator at the American Academy of Ophthalmology will be focusing on the SIGLEC trial for GA. Some critical insights the dual [inaudible] of AVD-104, as I mentioned before, targets the retina inflammation by modulating the immune cell over activation through targeting the repolarization of the macrophages to the resolution state and also activating the CFH activity to normalize the complement over amplification. I'm very excited to share the part 1 of the phase II/III trial the roll is completely done. This was happening over the last, you know, few weeks. We had a press release around it, and the ongoing phase II/III part 2 is active and starting to roll patients in the next few weeks for the second randomized portion of the study. What we're going to present and we will show, we will show preliminary part 1 data, and the highlight of the data showed sustained efficacy of AVD-104. In patient with GA, for the first time, we began to see in the majority of the patients some BVCA gain, best-corrected visual acuity using the etdrs chart, and also we saw stabilization and some patient also regression in the GA lesion over time.

As I said before part 2 of the study, which will be a multicenter, double-masked randomized trial to evaluate the treatment effect of AVD-104 in patient was GA against sham and active-control is active and enrolling patient the next few weeks. [There] will be close to 219 patient and the study going to be in US. One of the key data points I want to highlight and I will present in my talk during the American Academy of Ophthalmology will be the part 1 data we have generated thus far. What I can report, and I'm very excited about it as a retina specialist physician, we didn't have we didn't see any drug-related severe adverse events, either ocular or systemic. And we didn't see any evidence of those limits associated in any patient in any cohort in part 1 of the SIGLEC Phase II/III trial. Of interest, and also we look at this very carefully, we didn't see any drug related ocular inflammation, no retinal vasculitis, or neovascularisation infection for optic nerve abnormality in any patient in any eyes in your cohort in the phase, in the part 1 of the phase II/III SIGLEC trial. Also I can report, and I will report, no patient lost 15 letters or or more best-corrected visual acuity over 3 months.


However, not the, one of the key and and also the early efficacy data we have generated showed up to 80% in the majority of the patients analyzed thus far have reported best-corrected visual acuity gain after a single injection with AVD-104. And this was very clear dose response with the higher the dose, the more gain you see in these patients. Also initial data on the GA lesion hyper autofluorescence area, which was graded by a masked third party greater reading center, suggests stabilization and/or regression of the leading edge of the GA lesion.


So, in summary, we're very excited about the safety profile of AVD-104 in the clinic, that patient is, the drug looks very well-tolerated and safe at this moment was this early efficacy data is shown for the first time in GA space BCVA gain in patient was GA secondary MD and stabilization of the GA lesion is quite exciting, and we're very intrigued. And we're going to continue the development to the part 2, which is actively enrolling right now. And we will report more data in the upcoming clinical meetings or medical conferences in the next few weeks and the beginning of 2024.

AAO 2023: AVD-104 and the results of the phase II/III part 1 SIGLEC trial

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, PhD, Kerrie Brady, BPharm, MBA, MS, and Michael Singer, MD had to say!

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, PhD, Kerrie Brady, BPharm, MBA, MS, and Michael Singer, MD had to say!

ASRS 2023: Attendees share most interesting topics from annual meeting

Carl Regillo, MD, FACS, FASRS, spoke with our team following the annual ASRS meeting in Seattle, Washington to share insights from his presentation titled, "Modulation of Macrophages and Complement Dysfunction in Non-exudative AMD utilizing novel, sialic-acid coated nanoparticles."

I'm David Hutton of Ophthalmology Times. The American Society of Retina Specialists is hosting its annual scientific meeting this year in Seattle. Joining me is Dr Carl Regillo to talk about his presentation at this year's conference. Thank you so much for joining us. Tell us a little bit about your presentation.

Thanks, David. [I'm] happy to be part of this. My presentation titled, "Modulation of Macrophages and Complement Dysfunction in Non-exudative AMD utilizing novel, sialic-acid coated nanoparticles." Now, that's a lot. So [it] really describes a new mechanism of action of a therapeutic that's now in clinical trials for the treatment of geographic atrophy from AMD, in particular. 

So, what does all this mean? Well, we know that complement intubation has shown a reduction in GA lesion growth rates. We also know that the C3 C5 blockers that have been successful through Phase 3 trials have shown efficacy that have been rather modest. Plus, there's the side effect of secondary corneal neovascularization, which does appear to be a class effect. With a modest or limited degree of efficacy, it points to the fact that there's got to be another mechanism that is driving geographic atrophy. And indeed, there is evidence to suggest that the cellular arm of the innate immune response, namely macrophages, activated macrophages, play a role. 

So, there is evidence to show. Just like we're familiar with the deposition, or abnormal deposition, of complement in and around [inaudible] geographic atrophy and histopathologic studies. These studies also show an increased amount of macrophages, and there have been labeling experiments that show that these are actually pathologic or activated, so called activated macrophages. Macrophages exist in several forms, pathologic types, M1 [and] M2 for example, and then there's resolution resting or non pathologic types. 

The whole concept here with this therapeutic, called AVD-104, [is that] it's a cyanuric-acid coated nanoparticle. The nanoparticle is a bar-resorbable PLGA core, and it's injected individually. What happens is the sialic-acid binds to receptors on activated macrophages called siglecs. So when you bind the siglec on an activated macrophage it deactivates it, or so called polarizes it or cause it to resolve. The mechanism of action here is, in essence, to inhibit activated macrophages. There's another mechanism of action that was discovered in preclinical testing, which was ABD104, [It] also binds complement factor H, enhancing its inhibitory nature, and therefore dampening the alternative pathway. 

So, we got to do mechagnomes action, anti macrophage, and also blocking compliment to some degree. There's been a whole host of preclinical studies, in vitro human macrophages that show decreased macrophage cytokines like TNF-alpha and interleukin-12. It's shown to have an anti-complement activity in hemolytic assay. It's also been shown to reduce inflammatory retinal damage in a variety of animal models such as the light damage mouse model, and also decrease Mac formation in the laser induced CNV model. All this with good tolerability injected in variety of species, including non human primates, that is an individual injection. 

That leads us into where we are now, with AVD-104. It's in a Phase 2 3 clinical study called the SIGLEC trial. It's a 2-part study. Part 1 is a single dose escalation, individual injection for safety, with 3 months of follow up. Patients are being enrolled with multiple doses. We have data to suggest already that it's well tolerated, at least in the low and mid dose cohorts. We have patients that have been enrolled in these dose cohorts that have been followed up to 2 months and have not shown any problems with adverse events or serious adverse events. Once we're done with this dose escalation part 1 phase, part 2, the larger scale prospective, randomized clinical trial with ABD104 will start. We think that we're likely to get that started by the end of the year. So that's a 2 year, Phase 2 3 clinical study with both a sham and an active comparator control. This is a superiority study with the primary endpoint being the rate of change in geographic atrophy from baseline to 12 months as measured by fundus autofluorescence, which is the typical GA profile. 

So, in summary, we've got this very novel, unique therapeutic called AVD-104. It's a salic-acid coated nanoparticle with this dual mechanism of action that's performed well in preclinical studies, and is now in the early dose escalation part 1 of a 2-part, larger Phase 2 3 clinical trial.

Carl Regillo, MD, FACS, FASRS, spoke with our team following the annual ASRS meeting in Seattle, Washington to share insights from his presentation titled, "Modulation of Macrophages and Complement Dysfunction in Non-exudative AMD utilizing novel, sialic-acid coated nanoparticles." Aviceda Therapeutics is unlocking the proteogenomic code of AMD to target proteins and pathways linked to macular degeneration.  

ASRS 2023: Insights on AVD-104, a sialic-acid coated nanoparticle therapeutic for geographic atrophy

Paul Hahn, MD, PhD, spoke with our team about comparing the relative efficacy of pegcetacoplan versus avacincaptad pegol in patients with geographic atrophy at the 2023 ASRS annual meeting.

My name is Paul Hahn. I'm a retina specialist at New Jersey Retina. The purpose of this project was to try to compare relative efficacy of pegcetacoplan versus avacincaptad pegol. It's really an interesting time. 

We went from having no treatments for geographic atrophy, to having one approved treatment. Now, [we have] the possibility of another approved treatment for geographic atrophy all within the span of less than a year. So how do we decide which of these drugs to use? Well, in the absence of a head to head comparison, 1 thing that might be tempting is just to look at the top line data between the 2 trials. That, of course, is not something that you should do. 

A better way to do it is an analytical method called the anchored matched-adjusted indirect comparison. In this approach, called the MAIC, you try to match and balance the patient populations between the 2 different groups. So, you apply the inclusion and exclusion criteria from 1 trial to the other trial. Then you match or balance the populations by propensity score weighting to try to get as similar of a population between each group as possible. 

So in this trial, or in this study, patients from the pegcetacoplan studies, OAKS and DERBY, were filtered out to identify the same inclusion, exclusion criteria as from the avacincaptad pegol trial, called GATHER 2, only including patients that had non-subfoveal atrophy excluding patients with fellow eye, CNV, et cetera, and then balancing key characteristics like vision, lesion size, multifocal, et cetera. In the end, we found that when we compared pegcetacoplan monthly to avacincaptad pegol monthly, we found a statistically significant greater reduction with pegcetacoplan compared to avacincaptad pegol in OAKS, not in DERBY. But in a combined analysis, we also found a statistically significant greater reduction by 30% of pegcetacoplan monthly compared to avacincaptad pegol monthly when we compared pegcetacoplan every other month, in other words, less frequent dosing. 

Compared to avacincaptad pegol monthly, we found that although all the trends favored pegcetacoplan every other month, there was no statistical difference suggesting comparable efficacy. So, the overall conclusion of our study was that pegcetacoplan monthly appeared to show a better efficacy profile than avacincaptad pegol monthly in non-subfoveal GA patients. Every other month, or less frequent, dosing with pegcetacoplan appeared to show comparable efficacy profile to avacincaptad pegol.

ASRS 2023: Pegcetacoplan vs avacincaptad pegol in patients with geographic atrophy

Tarek Hassan, MD, spoke with our team about a novel glyco-mimetic nanoparticle for the treatment of geographic atrophy at the 2023 ASRS annual meeting.

Hi, I'm Tarek Hassan. I'm a partner of Associated Retina Consultants in Royal Oak, Michigan. I'm here at the American Society of Retina Specialists meeting in Seattle. 

Very excited to be here and present some of our early data using a new novel treatment paradigm, using glycobiology, glycoimmunology to try to treat geographic atrophy from dry AMD.

We are using a new compound that harnesses the body's own natural immune system to try to modulate the immune cells that directly are at the site of action of where the damage occurs in geographic atrophy. In our bodies, all of our cells are coated with things called sialic acids. They are sugars, and they're all over every cell. And those sugars are the immune model, immune identifiers to the actual immune cells. All different immune cells that have receptors that identify all of our cells in our body as either self or non-self; They're good or bad. So when these receptors on, for example, macrophages OR microglia, the immune cells that cause the damage and dry AMD, recognize damaged retina cells from the disease of macular degeneration, it turns on a whole process of inflammation, where the phenotype of macrophages that causes geographic atrophy turns on, and we figured out a way to present a drug to the eye that has sialic acids that mimic your own good sialic acids. So when the receptors come in, they meet our drug, and all the macrophages sort of stand down. They go from the activated state to the resolution state. And that happens for the phenotype of macrophages that causes dry AMD, and the phenotype of that causes wet AMD. The receptors, which are called siglecs, you'll hear that, you're going to hear that word more because it's the name of our clinical trial. Siglecs are simply the name of the receptors on all immune cells that recognize those sialic acids.

So our drug is a sialic acid mimetic. And by using it, we've been able to show in vitro and in vivo in multiple species of animals, great efficacy at reducing inflammatory cytokines, because we believe macular degeneration to be largely an inflammatory mediated disease, and also increase resolution cytokines. And we've been able to show significant efficacy, all the way up to now, hopefully, our human trials. So, we've introduced this siglec trial. It's phase 2/3 First, part 1 is enrolling now across the United States. It's a dose escalation study to determine our dose and biomarkers, and PK. We look to start enrolling our phase 2, or part 2 trial in the late part of this year, hopefully at the latest.

We have seen no safety signals whatsoever. There's no sign of inflammation in any animals that have been done in multiple species of multiple doses. We've seen no safety signals in the early clinical data that we've seen from the part 1 of the study, which was shown in a wonderful presentation by Carl Regillo, here at this meeting as well. So, we look forward to getting to talk to you more about siglecs, the receptors and silac acids in this new paradigm of glyco-immunology, using our own body's immune system, and the way it modulates inflammation, but we want to do it better with drugs that we can introduce into the eye.

ASRS Live: A novel glyco-mimetic nanoparticle for the treatment of geographic atrophy

Ursula Schmidt-Erfurth, MD, spoke with our team to share information on the GALE extension study at the 2023 ASRS annual meeting.

My name is Ursula Schmidt-Erfurth. I'm the Chairman of the Department of Ophthalmology at the Medical University of Vienna. I'm also the director of the Vienna Reading Center, and leading the ophthalmic Image Analysis Group, which is a computer science. 

Here at the ASRS, I will report about the extension of the OAKS and DERBY study, which are Phase 3 studies using pegcetacoplan treatment to limit the progression of GA [geographic atrophy] disease. There is an extension that has now started, the GALE study, which will continue up to 60 months. At the moment, we have the first 6 months of this extension available. The group of patients that is of highest interest for us [are] patients that were in the sham group over the 2 previous years of the Phase 3 study. These are lesions with very active disease. They have advanced quite substantially, and now they are rolled over to active treatment. 

This will give us insight about whether in advanced lesions, the complement inhibition will work. How do we measure this? We measure it by using AI based OCT analysis. We can identify the photoreceptor degeneration zone, which is a change at the level of the EZ [ellipsoid zone] line, and we can identify RPE [retinal pigment epithelium] loss. These are the 2 layers that are of relevance for disease activity and for the therapeutic effect. We found when patients crossed over, there was an immediate effect on photoreceptor preservation, which was almost 100%. That is quite a positive signal that even in advanced lesions pegcetacoplan treatment, anti-complement inhibition works very effectively. It also worked at the level of the RPE. There was a reduction by 19% in the progression of the lesion at the level of the RPE. 

Overall, this is very consistent [with] what we have found during the [inaudible] study, the Phase 2 and Phase 3 OAKS and DERBY studies, but now in advanced lesions and within only an observation of 6 months. This is a summary of the patients that had finished the Phase 3. 75% of patients did this despite the heavy COVID burden, and 85% of those patients have entered into GALE, so it's a significant number of patients. With these positive results, a tool was developed that is using OCT based AI analysis. It's called the GA monitor. It can be found on the Heidelberg AppWay, and it will allow clinicians in Europe, where the tool already has regulatory approval, to use this in clinical practice. [Also,] for the US colleagues, in an exploratory manner, to identify patients that do have disease activity, and that will also experience a therapeutic effect based on real data on photoreceptors and RPE.

ASRS Live: Gale extension study

Carl Danzig, MD, spoke with our team to share the exciting results of the GATHER 1 and GATHER 2 clinical trials for avacincaptad pegol for the treatment of geographic atrophy at the 2023 ASRS annual meeting. 

Hi, I'm Carl Danzig from the Rand Eye Institute in Deerfield Beach, Florida. I'm excited to be here at ASRS 2023 in the beautiful city of Seattle. I'm thrilled to be presenting a post-hoc analysis of vision loss in the GATHER program. Of note, I am a principal investigator, consultant, and speaker for Iveric bio.

In this clinical trial patients with extrafoveal geographic atrophy were entered to receive, entered in to the trial to receive either avacincaptad pegol or sham. And, in the GATHER 1 and GATHER 2 trials, both trials met their primary endpoint. What we saw in our post-hoc analysis is that patients who received ACP 2 milligrams avacincaptad pegol had a lower proportion of 10, 15, or 20 letter vision loss.

Furthermore, there was a 56% risk relative risk reduction of persistent vision loss in the treatment arm. What does that mean? Persistent vision loss is 15 letter loss over 2 consecutive visits. We also looked at patients who had persistent vision loss of 10 and 20 letters, and the trend was consistent. And for the first time ever, we were able to correlate vision loss with geographic atrophy growth. And what we saw is that, in patients with vision loss, the ones that did not receive treatment had greater GA progression in the ACP treatment arm, whether or not they had vision loss, there were lower rates of GA progression.

So in the ones that did not have vision loss, they had around a 2.1 millimeter squared GA growth. But in the patients who did have vision loss, the GA progression was far less than the ones who receive sham. So we're excited for the potential of treatment with ACP 2 milligrams to reduce GA lesion growth and, hopefully, have decreased rate of vision loss. Thank you again.

ASRS Live: Results of GATHER 1 and GATHER 2 clinical trials with Carl Danzig, MD

 EyeCon 2023 will gather the nation’s leading ophthalmologists to share new data and practical strategies that clinicians can apply in their practices. The conference will take place from December 1 to 2 at the Marriott Sanibel Harbour Resort and Spa in Fort Myers, Florida.

Cochair Peter J. McDonnell, MD, director of the Wilmer Eye Institute at The Johns Hopkins University School of Medicine in Baltimore, Maryland, recently spoke with 

 Group Editorial Director Sheryl Stevenson about what is unique at this year’s EyeCon 2023.

This transcript has been edited for clarity.

 We're joined by Dr. Peter McDonnell, who is with Wilmer Eye Institute, and we're so delighted to have you join us again as co-chair of our EyeCon conference in December, in Sanibel, Florida. 

I can't believe we're already talking about December and Florida in June and July, but no time like the present, right?

 I've heard time flies, and that may be true.

 We'd love to talk about this year's... looking ahead to this year's conference and what ophthalmologists should be really excited about or what you're most excited about in terms of some of the agenda?

The meeting is a great opportunity to get CME credits in one of the truly great settings. 

One of the things that I always remember, particularly when my children were young, was feeling really guilty going to one of these meetings and taking time away from my family. But when I brought my family to a place like Sanibel Island for a meeting, I didn't have to feel guilty because they would have a great time during the day while I was in the sessions. Then we could get together in the evening and they could show me whatever shells they'd collected and tell me about all the fun things they'd done, swimming in the ocean or the pool or whatever. It's an opportunity for a guilt-free way to update. 

There's so much innovation going on in ophthalmology that it's really it's impossible these days for anybody to read all the journals and see all the articles that are coming out. To have the opportunity to sit in a nice meeting, and with a very strong group of faculty, and have all the highlights in terms of innovation in our field presented and discussed about how to integrate them into one's practice would be a very cost-effective use of time and a really good way to make sure we're updated on all the things that are becoming available to us.

 Absolutely, you make some really great points there with that. In terms of focusing on some of the hot button topics, obviously, in ophthalmology right now. There's a lot going on with geographic atrophy. Do you want to talk a little about some of the events there?

Yeah, well, there's some big things, big FDA approvals that have recently occurred or will soon occur. 

You mentioned geographic atrophy, and you're exactly right. It's somewhere about 8 million people worldwide, 1 million in the US, that are going to be candidates for this new treatment that involves intraocular injections to treat this disease that until today, or until the launch of this new product, essentially we've not had anything to offer these patients. 

How are we going to treat? How we're going to take care of all these additional 1 million patients? How are we going to identify the patients that are the right, appropriate candidates for this treatment, educate them about their options, the costs, probably this is going to be a costly treatment. And then who's going to do all these injections and who's going to monitor these patients? And will it be retina specialists? Will it be comprehensive ophthalmologists? Will there be co-management with MDs and ODs to handle this enormous volume of patients?

Similarly, myopia... What could be a bigger public health impact than nearsightedness? And particularly in some subsets of our population, the prevalence of this problem has exploded. And so the recent FDA approval of devices for slowing the progression of myopia and the data suggesting that low-dose atropine can be very effective in reducing the magnitude of myopic progression in these young children means we're going to have to educate ourselves so we can educate our patients, or young patients and their families, about who's an appropriate candidate for some of these treatments for myopia. 

It's interesting about 80% of the literature on therapies, clinical trials for myopic progression have been not in the ophthalmic literature but in the optometric literature. That's an area where I think many optometrists may be, how would you say, more up on the latest literature in this area than the typical ophthalmologists. 

We want to make sure we're on the same page. Everybody's educated, and as patients come through our practices, many of which have both MDs and ODs in them, we're able to identify those individuals who may be appropriate candidates for these new treatments and plug them into whatever system we've created in our practice to deal with these patients. 

I'm sure every ophthalmologist that's listening to us has had the experience of parents coming in with their child, saying, 'we will do anything, we will pay anything if you can help our child not to develop this severe myopia that we have.' The parents often feel guilty. They know that it's often hereditary. They feel guilty that they quote, 'gave it to their child.' And they're eager for their child to have a better quality of life by not having this myopia be too severe or too much of a problem for them. Hence, the interest in orthokeratology, which I think will be small compared to the interest in some of the newly available treatments, including atropine, for these patients. 

I think it's a must for ophthalmologists to make sure they're up on the latest information when it comes to addressing progressive myopia in children. And that's something that'll come out of this meeting, and I'm very excited that people will leave and they will go back to their practices with that idea in mind [on] what to do for the coming new year on how to incorporate this into their practices.

I can't pick up a magazine or listen to the news these days without hearing about artificial intelligence. And there's all this new technology available in terms of home monitoring of diseases like glaucoma, where we can imagine that patients won't need to be filling up our offices anymore to come in for a quote 'routine' annual check of their visual field and their eye pressure to make sure to confirm that they're stable. 

But in fact, through use of some of this technology and artificial intelligence to interpret the results, we will be seeing those patients who maybe are having progression of their myopia and need to see us ophthalmologists because they need treatment. Or maybe they've developed diabetic retinopathy, and that was detected with one of the FDA-approved camera, artificial intelligence, diabetic retinopathy detection instruments that are proven to be quite sensitive and specific in detecting diabetic retinopathy. 

So we will be doing less of the what you might call regular annual checkups in diabetics, and instead we'll be seeing more of the patients that we know need some sort of treatment, because they develop some of the early signs of diabetic retinopathy.

Dry eye is another area condition just so prevalent. There have been some new recent approvals for dry eye. It pretty much used to be ointments and tears and then we had one FDA-approved medication for many, many years. Now we have an assortment of treatments that attempt to treat different forms or different kinds of dry eye, whether it's decreased tear production from inflammation, whether it's increased evaporation, whether it's eyelid margin disease contributing to the problem. We now have, as we would say, an armamentarium of potential treatments to help these patients who are often quite miserable. 

Cochair Peter J. McDonnell, MD, highlights what this year’s conference will mean for clinicians and addresses the anticipated increased patient volume.

Geographic Atrophy

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