Retina Society 2024: Advances in AMD therapy highlight different mechanisms of action with a common goal

David A. Eichenbaum, MD, highlighted interim results from the PRISM Phase 1/2 trial evaluating intravitreal 4D-150 in adults with neovascular age-related macular degeneration, as well as 12-month results from the DAVIO 2 trial, a Phase 2 multicenter study comparing a single injection of EYP-1901 (vorolanib intravitreal insert) with aflibercept in patients previously treated for wet age-related macular degeneration.

Eichenbaum presented his updates during the Retina Society 57th Annual Scientific Meeting in Lisbon, Portugal. He shares some of the highlights in this Ophthalmology Times interview with Sheryl Stevenson, group editorial director – eye care.

Video Transcript:

Editor's note: The below transcript has been lightly edited for clarity.

Sheryl Stevenson: We are joined today by Dr. David Eichenbaum, who is live at the Retina Society conference in Portugal. We're so delighted to have you, and we know you're giving two different talks regarding wet AMD, some different data points on different studies. So wanted to take a little time to talk about those top-level data coming from those talks. We'd love to hear more about the PRISM study and also the DAVIO study. Let's begin first with the PRISM study. What can you tell us about your talk?

David A. Eichenbaum, MD: Thank you, Sheryl, so much for having me. It's my pleasure to receive this invitation. I'm happy to give you an overview of the two presentations. Philosophically, these two talks are both looking at an unmet need in wet AMD, which is maintaining the excellent results we get with frequent intravitreal injections while reducing the injection burden.

The PRISM Phase 1/2 clinical trial is looking at an intravitreal gene therapy 4D-150, indicated in this clinical trial for patients with treatment experience wet macular degeneration. That trial enrolled a broad wet AMD population with a wide range of disease activity and antiangiogenic treatment burden in the Phase 2 interim results, focusing on the 3E10 dose, which has been the dose selected for the upcoming Phase 3 trial at week 24 showed a couple of interesting things. First, most importantly, that 4D-150 at 3E10 was safe and well tolerated. Second, that there were no serious ocular adverse events nor any clinically significant inflammation related to that dosing. All of the patients in the trial completed a prophylactic topical corticosteroid regimen on schedule. Importantly, there was durable clinical activity noted in this group. In Phase 2, there was an almost 90% reduction in the annualized anti-VEGF injection treatment burden, stable visual acuity, and sustained reduction in central subfield thickness [CST] stabilization and freedom from CST fluctuations. The Phase 3 trial, informed by those results, is starting in early 2025.

Now my second presentation is on the DAVIO 2 trial, which also aims to achieve the same goal of reduced treatment burden. This uses a different technology. This uses intravitreal tyrosine kinase. The EYP-1901 product studied in this program is a vorolanib in a polymer called Durasert E and that is compared to aflibercept 2 milligrams in this Phase 2 clinical trial. The DAVIO 2 Phase 2 trial is indeed the largest intravitreal tyrosine kinase inhibition trial we've seen to date, with one injection of EYP-1901 at 12 months. We showed that there was stable maintenance of visual acuity and strong anatomic control in this previously treated population. Half of all the EYP-1901 patients were supplement free; about a third of the aflibercept q8 week patients did meet criteria to receive supplements. The EYP-1901 reduced treatment burden by 80% versus pretrial treatment similar in number to the PRISM trial, which had an 89% reduction annualized treatment burden. And lastly, EYP-1901 was well tolerated with no ocular nor systemic adverse events of a serious degree related to the drug and no intraocular inflammation related to retinal vasculitis or severe drug-related adverse events. So it's a very safe product as well. And it's also moving into Phase 3, starting in the second half of 2024 and formed by the results of this Phase 2 trial. So two exciting technologies that I've had the chance to present, both of which are looking to meet the same goal with a different and diverse mechanism of action.

Stevenson: It's interesting you say that because obviously there is so much going on in wet AMD in terms of therapies and so forth and it's interesting to have these studies targeting the same goal, but with a different twist, right, with mechanism of action. What are your thoughts on that in terms of the importance of how a difference of mechanism of action can play in a study?

Eichenbaum: It's a great question. This is why we have Phase 3 trials in large, well-controlled populations to really see how these things work in a much broader sense. The nice thing about the tyrosine kinase product is it's a polymer, something we understand well, and it was very safe. The nice thing about the gene therapy is theoretically it's a one-time administration, and even though there's a lot to learn about gene therapy, there is a lot of promise there, with the potential for a single administration. Overall, the total injection burden is what matters. So I think in the phase 3 trials of these different technologies, which will be kicking off around the same time, we'll be able to see if there is a suggestion favoring one or the other, or perhaps for different patient subtypes, there'll be a preference for either tyrosine kinase inhibition or antiangiogenic transgene therapy. The nice thing as well in the real world is that technologies are complementary, and possibly the patients of 2027 or 2028 will be treated with gene therapy, tyrosine kinase inhibition, and very rare supplemental injections.