RWC 2024: Updates on the DAVIO-2 trial for EYP-1901


Ash Abbey, MD, spoke with Modern Retina at the 2024 Retina World Congress in Fort Lauderdale, Florida. He shared details about the week 32 data from the phase 2 DAVIO-2 trial for EYP-1901.

Ash Abbey, MD, spoke with Modern Retina at the 2024 Retina World Congress in Fort Lauderdale, Florida. He shared details about the week 32 data from the phase 2 DAVIO-2 trial for EYP-1901.

Video Transcript:

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

Ash Abbey, MD:

Hi this is Dr. Ash Abbey from Texas Retina Associates in Dallas, Texas. I'm at the Retina World Congress here, and I presented the top line data from DAVIO-2, which is a phase 2 clinical trial that is currently ongoing, but this was an interim analysis from week 32 data from the trial.

DAVIO-2 is evaluating something called DURAVYU, which is a conditionally approved FDA name for EYP-1901. EYP-1901, the active ingredient is called vorolanib, and vorolanib is a pan-VEGF receptor inhibitor. So it inhibits VEGF receptors 1, 2, and 3 intracellularly, and it also inhibits the PDGF receptor. So, obviously, inhibiting the VEGF receptors can reduce angiogenesis and vascular permeability, but the PDGF receptor possibly could also play a role in reducing progression to fibrosis. And then, it also does not interact, or does not actually inhibit, the tie-2 pathway, so allowing the tie-2 pathway to continue to function to maintain vascular stability. So, a little bit of a different mechanism of action from just our standard anti-VEGF medications.

It is being released in EYP-1901 through durasert technology, and durasert we've already been familiar with in the past with fluocinolone acetonide implants, like YUTIQ and Iluvien. The only difference here though, is that this is now a purely bioerodible matrix of duraset without the polyamide shell. The polyamide shell in Iluvien and YUTIQ remains in the eye after we after release, of course of 3 years of treatment with that, with that injection, the shell still usually remains. In this case, the bioerodible matrix in the durasert-e technology for EYP-1901. It erodes and degrades after about 9 months in the eye. And so there's nothing that remains after about 9 to 12 months in the eye from the injection. If we talk about the study design now, the patients in this phase 2 trial all had been previously treated for wet AMD, and they had to have had at least 2 and anti-VEGF injections in the previous 6 months prior to being enrolled in the study. When they were enrolled, the patients were randomized to receive either 3 mg EYP-1901, or 2 mg EYP-1901, or Eylea, every other month, a standard of aflibercept 2 milligrams every other month treatment.

All of the patients before they actually received their study treatment, whether it be their aflibercept or their EYP-1901, had to receive 3 total aflibercept injections to be run into the trial. And so on the third injection day of aflibercept for the treatment groups for the EYP-1901 groups, they also received EYP-1901 on the same day. So after that they were followed over the course of 56 weeks. And so we have, currently, the data cut off from week 32 to discuss in this presentation, but the patients will be seen monthly and in the EYP-1901 group they had rescue criteria, so that they could receive supplemental injections based upon both vision, presence of hemorrhage, and also anatomical measures on the OCT. Whereas the Eylea treated group, the standard of care group they would receive bi-monthly Eylea, but they also could be receiving supplemental injections on the months when they're not supposed to be scheduled for Eylea, based on those same retreatment criteria. What did the studies show? The primary endpoint at week 32 was looking at a change in best corrected visual acuity at that time between the mean best credit visual acuity of the treatment groups compared to the standard of care groups.

And what they found that there was there was not a significant difference between the 2 groups. So they found that statistically, there was non-inferiority in terms of vision changes among the all 3 groups, which is what their primary endpoint was designed to find. So they met their primary endpoint of statistically non-inferiority for vision change, and then also looking at the anatomy on the OST, they found at week 32, that there weren't any significant differences between the 3 groups with respect to central subfield thickness as well. The difference was roughly about 10 microns between the standard of care Eylea group and the EYP-1901 group. The interesting thing about the anatomy, though, that if you look at the actual graphs is that the Eylea group kind of has a sawtooth pattern over the course of the last few months of the trial. As the drug kind of waxes and wanes in the eyes, you see the anatomy kind of fluctuate with every treatment. Whereas the you EYP-1901 has something called zero order kinetics, and so it's constantly releasing the vorolanib over the course of that roughly 9 months that it's in the eye. And you can see that with respect to the an anatomical measure, because it's just a straight line of change over the course of the last 6 months over when it's being treated, compared to that sawtooth pattern that we see with the fluctuations with aflibercept.

Finally, when we look at the number of patients that required supplemental therapy, we can see that at the 6-month visit, basically 6 months after receiving EYP-1901, over 64% of the patients did not require any supplemental injections. And then if you look at the total reduction and treatment burden, it's roughly about 85 to 89% reduction in mean treatment burden compared to the prior 6 months before they entered the study. And then finally, we look at safety in this trial. The safety was, safety outcomes were all pretty acceptable overall. There was- there were no ocular serious adverse events that were related to EYP-1901 itself. The most common adverse events that were noted were vitreous floaters and worsening of AMD, but in low numbers. Conclusion here is that we have a potential for a lon- term therapy that has consistent release of this pan-VEGF inhibitor over the course of roughly 9 months that can supplement our current anti-VEGF regimen and allow us to potentially significantly reduce treatment burden in a safe way with just an extra injection in the office.

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