Advances in the Clinical Management of Diabetic Macular Edema and Age-Related Macular Degeneration - Episode 15

What’s on the Horizon for DME and AMD

August 12, 2022
Carl D. Regillo, MD, FACS

,
Blake Anthony Cooper, MD, MPH

,
Michael A. Klufas, MD

,
David R. Lally, MD

Carl D. Regillo, MD, FACS, leads a discussion with retina specialists about the future of care for AMD and DME, including tyrosine kinase inhibition and gene therapy.

Carl D. Regillo, MD, FACS: Mike, we’re living in an exciting time in our space treating these common retinal disorders, neovascular age-related macular degeneration [AMD], and diabetic macular edema [DME], some exciting new therapeutics and approaches to treatment but the pipeline looks pretty rich. There are other things coming. Tell me about it.

Michael A. Klufas, MD: The future is bright, no pun intended, and it can’t be lost upon us that gene therapy is approved in the eye for RPE65-associated inherited retinal dystrophy. We are using the same technology to create an ocular biofactory to create anti-VEGF in patients with neovascular AMD and diabetic retinopathy and diabetic macular edema. These programs with pars plana vitrectomy and subretinal approach are probably coming to us in the next couple of years if they pan out. The holy grail for gene therapy is determining if we can administer this in-office via suprachoroidal or perhaps an intravitreal approach. That remains to be seen. If aflibercept is something we are comfortable with, there is a high-dose aflibercept trial which may give greater durability based on the preclinical data, and we are all eagerly awaiting those results. Tyrosine kinase inhibition is another pathway that is not a biologic that we can administer at very high levels in the eye without causing systemic adverse effects. I don’t think it is being touted as a replacement for anti-VEGF, but perhaps a maintenance therapy with a vehicle that will allow continuous release in the eye. We also have some other exciting things such as OPT-302, which inhibits not only VEGF-A but VEGF-C and -D. That could be a nice compliment to something like faricimab, which inhibits angiopoietin-2, and we will see if other types of VEGF isoform inhibition may allow us to have better outcomes in some of our patients as well.

Carl D. Regillo, MD, FACS: A lot of what’s in the future is directly or indirectly targeting VEGF-A, maybe other mechanisms of action—VEGF-C and D; perhaps that’s going to get us better efficacy. The other approach is TKIs [tyrosine kinase inhibitors]; maybe durability. Gene therapy—the ultimate durability; we say 1 and done, but in reality it’s not going to be a cure. It’s not going to control disease in everyone across the board. Even phase 1 or at least testing is indicating it can do that to some degree in some people, but not everyone. There is a lot that’s unknown there, and I am sure we are going to be closely following the safety profile of the gene therapy programs, but it’s exciting and it’s not far off, as you indicated.

Blake, given the recent approvals for DME and neovascular AMD with some exciting new therapeutics or therapeutic approaches, what unmet needs remain both in the research and clinical treatment of these patient populations?

Blake Anthony Cooper, MD, MPH: Carl, it’s an exciting time to be practicing retina. We have a lot of treatment options for our patients, but probably the biggest unmet need right now is going to be the recruitment and diversity and generalizability of our upcoming trials. I feel that as we have better treatment options, it’s going to be harder to enroll patients, and we want to make sure that we are enrolling patients that are within our community. Creating networks within underserved communities and a more diverse pool of not only investigators and staff will hopefully help us be able to have trials that are more representative of the general population. I also feel that it’s important for us to make sure that we’re establishing long-term relationships within our communities and encouraging patients if they haven’t thought about a clinical trial to consider 1, because it’s going to benefit not only hopefully them but other generations of people who live with diabetes or macular degeneration.

Carl D. Regillo, MD, FACS: It’s an interesting point you brought up about the research in the diversity of the patients recruited into clinical trials. It is known; we have seen some ethnic differences in response to treatments. It’s going to be important. We make sure we could encompass all patients potentially affected by these conditions DME and neovascular AMD. Neovascular AMD in a Caucasian population can be quite different in Asian populations, and so forth. We've seen some differences there. In fact, some of those countries want their own clinical trials because of those differences.

Transcript Edited for Clarity

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