CTS 2024: 24 week results from the PRISM trials

Carl Danzig, MD, spoke with us about his presentation on the 24 week results of the PRISM trials for wet AMD. He gave this presentation at Clinical Trials at the Summit meeting in Park City, Utah on June 8, 2024.

Video Transcript:

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

David Hutton:

I'm David Hutton of Ophthalmology Times. Clinical Trials at the Summit is being held this year in Park City, Utah. Dr. Carl Danzig joins us today to discuss his presentation at this year's meeting. Thanks for joining us today. Can you tell us about the key points in your presentation, and their implications for ophthalmology?

Carl Danzig, MD:

Absolutely. David, thank you so much for having me. I'm really excited to present this important data this weekend at the clinical trials summit meeting in Park City. I'll be discussing the 24 week results from the PRISM trials, a randomized Phase 2, dose expansion stage, evaluating 4D-150 in high need, wet AMD patients. And I'm presenting a subgroup analysis of injection free patients.

The important thing to note about this trial is that it included the highest need patients that we have. Those patients had 6 injections or more over 12 months, they had to have fluid at screening with a baseline thickness of 325 or more. And the average thickness to enter the trial was over 400. So with this patient group, we know that when we want to look at molecules that control disease, we want to do it in the hardest to treat patients. And that's what we looked at here. So 4D-150 is a primate evolved intravitreal R1 capsid, that carries a dual transgene payload of aflibercept and VEGF-C RNAi. So as a single intravitreal administration, with a robust pan-retinal, trans-gene expression of four distinct VEGF family members. And what we saw in the trial was again, single injection, 50 microliters, it was safe. Okay, patients used only topical Darzalex prophylaxis. And 38 out of 39 patients did it without needing any bump up, only one patient during the taper had to be bumped up on their steroids due to mild anterior inflammation. Okay, and that resolved. No patient had to be restarted on any steroid regimen, after they tapered it off, up to 48 weeks.

Furthermore, what we saw in this high need patient population was a reduced injection burden with an 89% reduction. And 63% of the patients were injection free. We saw excellent anatomic control. We saw sustained reduction in retinal thickness and stabilization of CST. That's in comparison to that normal seesaw pattern we see in the aflibercept arm that's treated every 8 weeks. And furthermore, in these high need patients, in the ones that were supplement free, so they had their injection of 4D-150 at baseline, and they went 24 weeks without needing any injection. They had excellent anatomic control in the 3E10 arm. And every time point was below the aflibercept even at the trough of the seesaw. So this is really encouraging.

Furthermore, we've seen from the Phase 1 patients that there's some of them that went up to 2 years, so we see durability. And this is very exciting for our patients, because we're always looking for what can we do more for our high need patients and and this is what we have and we're looking forward to finishing the Phase 2 trial and hopefully starting a Phase 3 trial in quarter one of next year.