Prospective Therapies and Treatment Strategies for nAMD

Opinion
Video

Experts discuss prospective therapies and improved outcome targets for patients with neovascular age-related macular degeneration (nAMD).

Transcript

Ehsan Rahimy, MD: Jon, you made an interesting comment earlier. At least in 1 respect, you mentioned oncology. Our field has always had this hope that retina is oncology 2.0, with newer therapeutic targets targeting different mechanisms of action. You also mentioned that the bar is incredibly high. Is this as good as it gets? We’ve seen many failures in the clinical trial around late-stage testing. Some of our colleagues have speculated that this is as good as it gets, and that a lot of what we’re seeing on the trial end is more of a durability game than anything. Maybe it’s smoke and mirrors. What do you guys think?

Veeral Sheth, MD, MBA, FASRS, FACS: That’s tough. I don’t want to believe this is as good as it gets. We’re hopeful. Knowing what’s in the pipeline, there’s a lot of expectation that we’re going to make progress. Someone mentioned gene therapy earlier. Durability isn’t just reducing treatment burden. It’s also modifying disease. That’s the way I look at it. Even if you’re still approaching it as an anti-VEGF, you’re able to give it in a way that over the long term—a year, 2 years, longer—you can modify disease. That’s something we haven’t thought about as much because of the way we give drugs and the bolus effect of how we give it. The short answer is no, I don’t think this is as good as it gets. We move forward from here.

Jonathan Jonisch, MD: I’ve given this a lot of thought. It’s tough to wrap our heads around when we analyze clinical trials. We know that when a patient comes into our office with a specific disease, not all patients are able to get to 20/20 [vision], no matter what we do. From a population-based medicine approach, we have to do a better job of educating the general population because we need to catch these diseases sooner.

When we have comparative trials of all these medicines, a lot of times it has more to do with the patient’s disease than what agent we use. There are definitely agents that last longer. There are probably some agents that are superior to some of our other agents. But the bottom line is the patient’s disease, and the time at which they presented usually is the leading indicator of how their vision is going to be. Their vision [going] in is the best predictor of what their vision at the end is going to be. We need to do a better job of coming up with better therapies and [using] dual-mechanism. We have to reduce atrophy in our wet AMD [age-related macular degeneration]population, but we have to get patients into our office sooner in their disease process to make a dent and go further in what we’ve accomplished.

Ehsan Rahimy, MD: That’s a great point. Ali, any parting comments for this section before we close it out?

Ali Khan, MD, FACS, FASRS: We were used to thinking of outcomes in aggregate, across an entire trial or database, but not necessarily in terms of the individual patient. There’s still a lot to learn [about] perhaps any racial or ethnicity differences that might affect treatment outcomes, or perhaps drug choice or algorithms. None of our clinical trials is powered to make that decision-making or give us those types of insights. There are a couple of phase 4 trials looking at treatment outcomes in specific patient populations based on race and ethnicity. These other issues are going to become more part of our discussions, which is a good thing. In the cardiology world, there’s quite a bit of data showing that outcomes can vary drastically based on race and ethnicity. Who’s to say that’s not true in ophthalmology, particularly in patients with diabetes? It feels as if we’re reaching a ceiling, but it’s because we’re going to be asking you questions. That’s a good thing overall.

Veeral Sheth, MD, MBA, FASRS, FACS: One extra point on that is the more options that become available, the more we’re going to be able to personalize the treatment approach. Oncology does this all the time, where you’re using a different cocktail of treatments to approach a patient. We’re just starting to figure out what formula is going to work for this individual patient. We’re coming from a world where we used Avastin [bevacizumab] on everybody. We’re starting to evolve our own thinking and our own approach to each individual patients. That’s another phase of this personalized approach that’s going to change things for patients.

Jonathan Jonisch, MD: One area where we have to do better overall is racial equity. We know African Americans do worse in the real world compared with other ethnicities. And not only that, but their representation in our clinical trials also remains really low. Those of us recruiting for clinical trials struggle with trying to improve those numbers and recruitment in that population to have better data on how they do in these trials. That’s a point. When we look at the population, some of the ethnicities and racial demographics that can be improved could lift the aggregate.

Ehsan Rahimy, MD: [This has been a] wonderful discussion on AMD. That concludes this section of our discussion.

Transcript edited for clarity.

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