WIO 2023: ZETA-1 phase 2 trial safety and tolerability results for APX3330

Priya Vakharia, MD, spoke with our team about her presentation at the Women in Ophthalmology Summer Symposium being held in Marco Island, Florida.

Video Transcript

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

Sheryl Stevenson:

We're joined today by Dr. Priya Vakharia who is presenting at this year's WIO or Women in Ophthalmology conference in Marco Island, Florida. Welcome to you. We're so delighted to have you. And so curious to hear about an update on the novel ref-1 inhibitor for the treatment of diabetic retinopathy. Can you tell us about your presentation?

Priya Vakharia, MD:

Thank you. Thank you so much for having me. So my presentation focuses on an oral pill that can be used, that was used in a phase 2 trial to see if it could prevent progression of diabetic retinopathy. So first, let's talk about a little bit of background when it comes to the treatment of diabetic retinopathy. We've had a lot of studies in the retina space showing that anti-VEGF injections can be given to patients at regular intervals, and that, you know, helps with progression of DRSS scores, or diabetic retinopathy severity scores. And so we know that anti-VEGF injections work, but this is a novel mechanism looking at an oral pill that inhibits a transcription factor called rev-1. And this transcription factor is actually upstream in the cascade of inflammation in angiogenesis. You know, further downstream we have our more common VEGF molecule, but this is much more upstream in that cascade to see if by taking this pill, can you get similar results in terms of improvement at DRSS. So this was a phase 2, randomized, placebo-controlled trial, in which patients got randomized 1:1 to either get APX3330, which is the ref-1 inhibitor versus a placebo control. And so there were 103 patients in the study. And in this study, you know, the primary endpoint was looking at two step improvement in diabetic retinopathy severity score at week 24. That's the typical endpoint that we've historically been looking at with anti-VEGF studies. And at week 24 patients on the APX3330 arm had the same percentage of improvement of that two step DRSS compared to placebo. So this study did not meet its primary endpoint. However, when you look at the patients who actually had worsening, so three step worsening of DRSS, none of the patients in the APX3330 arm had worsening. Whereas there were patients in the placebo arm that had worsening specifically there were 16%. And so that brings up the question that perhaps this inhibitor is, while it may not be improving disease, perhaps it's preventing worsening, and the theory makes sense, because this ref-1 inhibition could just promote physiologic VEGF states rather than decreasing it like our traditional anti-VEGF. And so that's the summary of the study.

Sheryl Stevenson:

It's fascinating, really that research. Is there anything else that you'd like to add that we haven't even touched upon?

Priya Vakharia, MD:

I think the next steps for this study would be to go back to the FDA for the phase three and see if this is an approvable endpoint, you know, this is three step worsening. This is binocular three step worsening, which I didn't mention before. So there is a meeting slated with the FDA to see that if to see if the binocular three step worsening could be an approvable endpoint for a phase three trial. So those are kind of the next steps from here. And we look forward to updating everyone as as that information becomes more clear.