Key takeaways from the DAVIO 2 study with Rishi Singh, MD

Rishi P. Singh, MD, recently sat down with Modern Retina to share a few of the key takeaways from the phase 2 DAVIO 2 trial (NCT05381948) evaluating EYP-1901 for the treatment of neovascular age-related macular degeneration (AMD), which he presented at the Macula Society 47th Annual Meeting in February 2024.

Study structure

EYP-1901 is a pan–VEGF receptor inhibitor from EyePoint Pharmaceuticals. In the trial, EYP-1901 was compared with aflibercept. After 3 loading doses, the patients were randomly assigned to receive EYP-1901 or continue to receive aflibercept at an 8-week dosing pattern for 32 weeks. The study is set for 56 weeks overall, meaning there will be a long-term outcome from the study as well.

Key takeaways

• An advantage of EYP-1901 is the ability to inhibit all the VEGF receptors—1, 2, and 3—without inhibiting VEGF type 2 at the clinically relevant doses.
• Best-corrected acuity, which was the primary end point, was stable over 6 months.
• It was reported that 64% of eyes were supplemental injection-free up to 6 months.
• It was also reported that 85% of participants had a mean reduction in treatment burden, compared with the 6 months prior to randomization, which demonstrated the product’s ability to potentially reduce the burden of treatment for patients.
• The visual acuity was largely stable for the entirety of the study, as was the central subfield thickness. Singh noted that there were good signals to show that there was no significant concern about this drug not working appropriately in this 6-month period.
• There were no ocular serious adverse events reported related to
  EYP-1901 overall.

Watch the full interview below.

Video Transcript

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

Sydney M. Crago: Hi, I'm Sydney Crago with Modern Retina, and today we're here with Dr. Singh to talk a little bit about the DAVIO-2. trial by EyePoint for wet AMD. Dr. Singh, could you share a little bit about this trial?

Rishi P. Singh, MD: Yeah, thank you. This is an interesting study of patients who are receiving this EYP-1901. One, this is a pan-VEGF receptor inhibitor called vorolanib. We're all familiar with Durasert technology. It's been prior steroid therapies for macular edema, for diabetes, and we've used in the past, and it's fully by erodible. And that's a really advantage of this technology overall. And the other advantage of this product is really the ability to inhibit all the VEGF receptors: 1, 2 and 3, without inhibiting type 2 at clinically relevant doses.

When we look at this drug in the study of DAVIO-2, it was compared to receiving aflibercept. After 3 loading doses, basically the, at that point in time, the patients were randomized to receive either 1901 or continue to receive aflibercept and an eight-week dosing pattern for a period of 32 weeks. This is a 56 week study, and there will be a long-term outcome from the study as well.

And what the study was able to do through retreatment criteria is show how many patients were needing supplemental retreatment with aflibercept during in the course. Now, these were previously-treated patients, these are patients who actually had prior treatment anti-VEGF. And they were essentially, from a retinal thickness standpoint, controlled, and they had a retinal thickness of less than 350n prior to entry.

And what the study essentially found was that the number of patients requiring rescue at 6 months was around 64% of patients not requiring rescue. And again, the amount of injections given prior to randomization decreased by 89%. So again, showing you a good benefit as far as the ability for this drug to potentially reduce the burden of treatment for the patient population. Of course, because it's the previous-treated population, the visual acuity did not really increase very much, it was pretty much stable the entirety of the study. And the central subfield thickness, again, was stable, which again, are good signals to show you that there is no significant concern around this drug not working appropriately in this 6 month period of time.

Again, from the standpoint of a safety, we are always concerned about safety overall. And we found essentially that this drug was very safe, there were no ocular, serious adverse events are reported related to this EYP-1901 overall. And there were some other events that reported just from the intravitreal injection practices that we all sort of take.

So, just to summarize, again, we saw very strong anatomical control with EYP-1901. Their best-corrected acuity, which was the primary endpoint, which was stable over a 6 month period; 64% of eyes were supplemental injection free up to 6 months, and 85% at a mean reduction in treatment burden, compared to the 6 months prior to randomization. And again, because of the favorable safety results, this is going to continue into the 56-week study showing again, hopefully, some benefit to our patients.

In practice. How does this impact impact what we're doing? One of the biggest concerns or issues around anti-VEGF therapy is really the burden of treatment. It requires, obviously, multiple offices. It requires time in the office with the physician. It requires transportation to and from, and a patient population, some in DME and some and AMD which are still working and have significant need to reduce the burden overall. And patients don't get nearly the number of injections in the real world we expect them to get until they fall off the visual acuity curves. Their anatomy doesn't always respond to therapy as a result of not getting enough injections. And therefore this technology may offer hope and reducing the burden overall of patients getting these drugs from the standpoint of controlling their macular degeneration better or controlling their diabetic macular edema better as well.