ASRS 2023: The evolution of treatments for dry macular degeneration

The American Society of Retina Specialists is hosting its annual meeting this year in Seattle, Washington. Our team caught up with Baruch Kupperman, MD, PHD who is presenting, "Improving vision and dry AMD matching mechanism with the right patient population and stage of disease" to learn more about this topic.

Video Transcript

Editor's note - This transcript has been edited for clarity.

David Hutton:

I'm David Hutton of Ophthalmology times. The American Society of Retina Specialists is holding its annual meeting this year in Seattle, and our team will be providing all of the latest content you've come to expect. Joining me today is Dr Barry Kupperman, who is presenting, "Improving vision and dry AMD matching mechanism with the right patient population and stage of disease." Thank you for joining us today. Tell us about your presentation.

Baruch D. Kupperman, MD, PhD:

Thanks, David. It's my pleasure to be here and sharing this information with you. I'm Barry Kupperman, director of the Gavin Herbert Eye Institute at UC Irvine, and I'll be presenting the material at ASRS. I'm a consult to the companies involved with this. It's primarily work provided by Allegro, and I'm a consultant to them as well as Stealth BioTherapeutics, and I'm a consultant to them as well.

The important part here is, as we're seeing the evolution of treatments for dry macular degeneration, the focus has been with complement inhibition. Of course, we've seen the work from Apellis, and when they're C3 inhibition and IV5 with their C5 inhibition, but that's to treat geographic atrophy. There are companies and products that are looking at earlier disease states before geographic atrophy is present, or even when it is. In particular, they'll be presenting some work by Allegro with on their compound Risuteganib, which is an integrin peptide modifier, and the cyanogen peptide regulation, as it does seems to work on the level of the mitochondria. [inaudible] Stealth Therapeutics has its own mitochondrial membrane stabilizer. What they have in common is trying to look earlier at disease.

The FDA has mandated that earlier in disease, it's not necessarily appropriate to look for progression of anatomic finding i.e. geographic atrophy. But, honestly that is in some debate with the FDA as to whether a micro geographic atrophy would be enough. So, nearly no geographic atrophy, but if you're looking absent geographic atrophy, the FDA has mandated that we need to show improvement in vision. Of course with geographic atrophy, we're not being asked to show that at all, just slowing down the rate of the lesion size. It was enough for approval for Apellis's compound, Syfovre and presumably will be appropriate for Zimura, Iveric Bio's compound, different for this class of drugs.

Again, everything is somewhat under debate with the FDA, though, they've made their lines pretty clear. So, if you're looking to improve vision, how do you properly select. First of all, mitochondrial membrane stabilization, or adjusting the mitochondrial membrane in some way, may be providing not just a neuro protective effect, but we're looking for a neuro enhancing effect, ie improving vision distortion, because that is what it appears that the FDA is asking for. But even then, if you look at the data from the studies that have been generated already, and looking retrospectively with post hoc analyses, there's risks. They've been able to identify several factors that may predict the appropriate population that is capable of improving their vision.

So, it is a way to enrich the patient population for studies going forward. The criteria that they found [is] broad enough that it looks like it may be appropriate for other compounds as well, not yet studied. Basically, a lot of this is the work coming out of Justis Ehlers at [the] Cleveland Clinic Cole Eye Center and Glenn Jaffe from Duke. They've been able to look, anatomically, very carefully and looking at the ellipsoid zone. If there's enough ellipsoid zone preservation on OCT, then it looks like those are the patients that may show be able to show an increase in vision, which is being asked for by the FDA for these compounds, and therefore would be the patient population you'd like to study going forward. This is a finding. There's other features too. Looking at other things race, gender, sex, etc, none of those were predictive. But, when you looked at specific anatomic features, less so some of the functional things, [like] microperimetry, you can see what the responders look like. But, that's not as predictive as if you look at the OCT findings, then map out [it] well with microperimetry, then progressing and improving.

So again, the important message here is the challenge that's been put to us by the FDA is to show neuro enhancement, ie improvement, in vision in a patient population that is earlier than geographic atrophy with intermediate dry macular degeneration. By looking at the ellipsoid zone, we seem to have identified the population that is the one most likely to benefit from these products. This is the primarily from Allegro and their compound Risuteganib, but it seems to correlate with data from Stealth Therapeutics with their compound Elamipertide.

David Hutton:

What are the next steps for this research?

Baruch D. Kupperman, MD, PhD:

I think it's going to be in the design of the trials going forward, there's further corroboration being done. The anatomic findings, in particular, were corroborated between Duke and Cole, but even other companies and other compounds are paying attention to this and have also looked at this sort of data. For example, jCyte, another company that I consult for, has retinal progenitor cells that they're looking at for the treatment of retinitis pigmentosa.

They're also looking at OCT features at the population to be the ones most likely to benefit from therapy. I think what this really does for patients is provide the companies a clear identification of the patient population that would benefit and as a result that is more likely to get these promising products into the marketplace, where they can be further distributed to patients on a wider scale.