Roger A. Goldberg, MD, MBA, presents a post hoc analysis of the Phase 2/3 PHOTON trial, offering insights into the potential benefits of 8 mg aflibercept in managing fluid reaccumulation, particularly in cases of diabetic macular edema.
Roger A. Goldberg, MD, MBA, recently spoke with Ophthalmology Times Group Editorial Director Sheryl Stevenson about a post hoc analysis of the Phase 2/3 PHOTON trial. He provided insights into the potential benefits of 8 mg aflibercept in managing fluid reaccumulation, particularly in cases of diabetic macular edema, in his talk at Hawaiian Eye and Retina 2024.
Editor's note - This transcript has been edited for clarity.
Sheryl Stevenson: We're joined today by Dr. Roger Goldberg, who will be presenting at this year's Hawaiian Eye and Retina meeting. Welcome to you. So delighted to have you and really curious to learn more about your talk. I know you're going to be speaking more about the post hoc analysis for the Phase 2/3 PHOTON trial. Can you tell us more about that?
Roger A. Goldberg, MD, MBA: Sure! Thanks, Sheryl. Thanks for having me. And it's great to get to present at Hawaiian Eye and Retina in Maui 2024. My talk is actually on looking at a post hoc analysis of the PHOTON study, which was the pivotal study for Eylea HD (aflibercept 8 mg) given every 12 or 16 weeks after three loading doses versus 2 mg aflibercept given kind of on label with five loading doses followed by every 8-week treatment.
We know, of course, from the topline data from PHOTON that it met its primary endpoint, that 8 mg aflibercept given every 12 or 16 weeks was noninferior visual acuity to 2 mg aflibercept. And we also know that the mean central retinal thicknesses across the first year of this study were very similar across all three arms of the study. But what we wanted to look at was really to dig deeper into the those hardest-to-treat eyes, the eyes with the most fluid at baseline.
So what we did is we divided up all the patients at baseline into quartiles, based on their central retinal thickness. Q1 had the thinnest retinas under 360 microns, and Q4 were the thickest, the most swollen retinas, those were over 528 microns at baseline minimum. And actually, if you look at the average of this group, you'll see it was around 610 to 640 microns of central retinal thickness.
Not surprisingly, Q4 (the fourth quartile group) also had the worst visual acuity about 55 letters, on average, across the three arms. They are otherwise well balanced. And importantly, when we look kind of across all four of these quartiles, we saw again very similar visual acuity and central retinal thickness curves, but not surprisingly, in quartile four, that's where we see the most fluctuation in fluid across all the arms of the study, including the 2 mg aflibercept arm.
We dug in a little bit more closely into this fourth quartile (most swollen retinas) and I think this is some of the best data we have actually to support the longer durability of 8 mg aflibercept versus 2 mg aflibercept. And when you look at these difficult-to-treat eyes, after the five loading doses in the 2 mg aflibercept eye, the fluid reaccumulates, not surprisingly. And so what we see is in the 2 mg-treated eyes, 8 weeks after their last loading dose, 55 microns of central retinal thickness of fluid has reaccumulated whereas—from the last injection—versus in the 8 mg of aflibercept arms, both the q12 and the q16 arms after their three monthly loading doses, only 5 microns of fluid has recollected.
So it really shows that the 8 mg aflibercept is preventing the reaccumulation of fluid at a much better rate in these most difficult to treat eyes. And I think those are the eyes we're most passionate about moving to our next-generation therapies. So, again, very compelling data in DME [diabetic macular edema] for these difficult to treat, very swollen eyes, that we can slow down the reaccumulation of the fluid, significantly better with 8 mg aflibercept versus 2 mg aflibercept.
Stevenson: Thank you for that quick summary of your talk. I wonder what might be the next step in the research or approach for this therapy then
Goldberg: As you know, it's being now used clinically both in wet AMD and diabetic macular edema. And I think it'll be fascinating to look at the real-world evidence to see, hey, can we shift the interval between treatments as we migrate patients from 2 mg aflibercept to 8 mg aflibercept. And so it's probably a little bit early to get much in the way of real-world evidence at this point but I would think kind of coming forward in 2024 we'll get a look at that.