ANTI-VEGF for WET AMD: DAVIO 2

Dr. Kondapalli: The first study that we’ll talk about is the DAVIO 2 study, which was a phase II randomized prospective clinical trial that looked at a single injection of EYP-1901. This is an investigational drug from EyePoint Pharmaceuticals. The investigators compared it at two different doses versus aflibercept, or Eylea, which was the control arm. EYP-1901 is a tyrosine kinase inhibitor, and that molecule is contained in a sustained-release polymer, which is injected intravitreally, very similarly to traditional intravitreal injections.

Enrollment criteria

Patients were enrolled on the study who already had undergone treatment for wet macular degeneration, or neovascular AMD. And what’s unique about this, compared to perhaps some of the other trials with anti-VEGF agents that we’re familiar with, is that, in the DAVIO 2 study, the patients were not treatment-naïve. They had received at least two anti-VEGF injections 6 months prior to enrollment.

Randomization

They were randomized to one of three arms: a single low-dose arm, so that was at 2 mg of EYP-1901; a high dose arm, which was 3 mg of EYP-1901; or the control arm, which was aflibercept administered per the on-label dosing of every 8 weeks. Initially, patients all received 3 monthly aflibercept doses, and those were basically their loading phases every month, so at 0, 4, and 8 weeks. But, those patients who were receiving the investigational drug received an additional EYP injection at the third and final visit, basically at week 8. What was interesting to note is that those patients in the investigational arm were able to receive supplemental aflibercept injections, and this was one of the endpoints that we were looking at: what percentage of patients required supplemental treatment?

Primary endpoint

The primary endpoint in DAVIO 2 was the mean change of best-corrected visual acuity from baseline to weeks around 28 to 32. And that basically represents about 6 months after the first and only EYP injection. The DAVIO 2 study met its primary endpoint in the sense that it showed a noninferior mean change in best-corrected visual acuity from baseline at weeks 28 to 32.

Six months in and no need for supplemental aflibercept

What was more interesting, though, is that about 64% of patients in both investigational arms, both the low dose and the high dose arm, did not receive any supplemental aflibercept injections at week 32. Two-thirds of patients did not receive any additional treatments at 6 months as well.

In terms of follow-up, there’s going to be a phase III trial that is currently enrolling and will continue to enroll throughout 2024.