Updates from Angiogenesis 2025 meeting detail recent outcomes for EYP-1901 in AMD and DME

Carl Regillo, MD, director of the Retina Service at Wills Eye Hospital and a partner at Mid Atlantic Retina in Philadelphia, details study outcomes presented at the Angiogenesis 2025 Meeting.

Question:

You recently gave a presentation at the Angiogenesis 2025 Meeting titled “EYP-1901 for Retinal Exudative Diseases, Phase 2, Davio 2 nAMD End-of-Study Results, and Phase 2, Verona DME Results.” What were the findings from the phase 2 end-of-study DAVIO 2 data? What were the outcomes from the phase 2 Verona study?

Carl Regillo, MD, FACS, FASRS:

At the Angiogenesis meeting, my presentation was 2 parts, EYP-1901, the end-of-study, large DAVIO 2 wet AMD study results and the interim DME phase 2 Verona results. For the wet AMD results, the performance of EYP-1901 in eyes that were previously treated for wet AMD, it performed very well as maintenance phase therapy. Introduced at 1 of 2 doses, one-time administration with patients then followed over the course of 12 months after the administration or 14 months end of study. Two doses, those 2 arms compared to aflibercept on-label dosing every 8 weeks.

In this clinical trial, all arms could receive aflibercept rescue therapy per protocol-specific re-treatment criteria. What it showed, it showed excellent BCVA outcomes in both EYP arms out to the primary endpoint, which was averaged month 7 to 8 and then all the way to the end of study, that’s month 13, 14. Again, that represents 12 months after the EYP dosing. This was a noninferiority study and it met its primary endpoint with both doses.

All the way through the end of the study, we saw nearly identical best corrected visual acuity outcomes compared to bimonthly or every other month aflibercept dosing over the course of the study. Very impressive vision outcomes. When you look anatomically looking at OCT outcomes, we saw a very good disease control with very level OCT in both arms, unlike what we tend to see when we do bolus injections of every other month dosing, for example, with aflibercept where you get that classic sawtooth fluctuation with the central subfield thickness and OCT. But also very important is disease control with very little supplementation or rescue treatment needed over the course of the entire study. When you look to the primary endpoint, two-thirds of patients in the 2 doses of EYP were supplemental injection-free. About one-third needed supplements, two-thirds did not need through 6 months after the single EYP administration. As we get into about 1 year, almost about half of the patients not requiring any supplements.

Two-thirds of patients can go 6 months without the need of supplement with good disease control, again, as evidenced by the outcomes by BCVA and OCT. Just under about a half made it 12 months after the single EYP administration. What this did translate into when you compare these patients before they were involved in the clinical trials, because they’re all previously treated, and most were very frequently treated, averaging about 9 to 10 in the year before, that’s the annualized mean number of injections in both dose cohorts. We’re seeing about an 80%, 81% reduction in treatment burden. That’s exactly what we expect and hope that a sustained-release maintenance phase therapy should do.

Now for the Verona, that’s the DME phase 2 study. Smaller scale, unlike the wet AMD study, which is actually the largest TKI study for wet AMD to date, and now in phase 3 testing, the Verona is more of a, do we have a signal at a phase 2 level looking at 2 doses of EYP in patients with center-involved DME compared to aflibercept.

In this study, all patients received a single aflibercept injection, and in the 2 EYP arms a single EYP injection, and the primary endpoint was 24 weeks. But what I presented was the interim 16-week outcome, and it looked really positive with a strong signal for efficacy of EYP single injection improving the vision. BCVA improvements were seen fairly impressive at the high dose at around 9 letters and about 4 letters comparable to the single aflibercept injection control arm at week 16. That’s 4 months after the administration of a single injection of the anti-VEGF aflibercept with or without the EYP. EYP at a high dose worked well to improve the visual acuity compared to baseline in patients with center-involved DME. Looking at OCT, of course, we saw a very good reduction in central subfield thickness after just the 1 administration. Very promising type of clinical benefit for patients with center-involved DME with EYP-1901.

Over the course of those 4 months, very few patients received any supplemental treatment. Right through that 4-month endpoint, that interim endpoint, 82% of the high dose were injection-free, meaning no supplements, and that’s the high dose, 60% at the lower dose and with aflibercept single injection control arm, 50% were supplemental free, so half needed some supplements by 16 weeks. What I didn’t present at Angiogenesis is right before the meeting, there happened to be a press release in which we saw the final 24-week data, and it also looked very positive. About three-quarters of patients in that high dose were injection-free 6 months after the high dose of EYP administration. Holding up very well, both in terms of what I presented for an interim results and subsequent press release for further follow-up in that Verona study.

Question:

What are the key takeaways from the presentation for clinicians?

Carl Regillo, MD, FACS, FASRS:

We’re looking at a TKI product here. It’s an intravitreal administered polymer insert that looks to be controlling wet AMD in the maintenance phase. That is patients that have previously treated very well in addition to seeing a strong efficacy signal for DME. We’re in phase 3 testing already and within the next couple of years we’ll have the results to know precisely how safe and effective the insert is for patients with wet AMD either previously treated or treatment-naive. We’re highly likely to see this product also move forward with further testing in DME, either previously treated or treatment-naive is highly likely to be looked at in that disease state too. I should mention that up through phase 2 testing, phase 1 and phase 2 for both disease states, the insert is very well tolerated and there have not been any serious adverse events related to the product, and so very well tolerated to date, which is very, very encouraging.

Question:

How might vorolanib intravitreal insert, an investigational sustained delivery therapy, change the therapeutic field for DME?

Carl Regillo, MD, FACS, FASRS:

Well, I think there’s a strong chance, of course, contingent upon a successful phase 3 outcome, for both wet AMD and DME that will be using such a product for patients to decrease the treatment burden. In other words, for patients that require frequent injections of traditional anti-VEGF agents for either wet AMD or DME, this could be introduced as a sustained delivery in the maintenance phase to reduce the need for injections and get the same or nearly the same types of vision outcomes.