ARVO 2025: Shortened, maintained, or extended dosing intervals through 96 weeks in PHOTON

At ARVO 2025, in Salt Lake City, Utah, Dilsher Dhoot, MD, FASRS, and Mark Barakat, MD, talked about the PHOTON trial, 8 mg versus 2 mg during the matched dosing phase, and outcomes of shortened, maintained, or extended dosing intervals

Video Transcript:

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

Dilsher Dhoot, MD, FASRS:

Hi, I'm here at ARVO 2025, and I'm presenting a poster for EYLEA HD and looking specifically at the PHOTON data. This is a post-hoc analysis. As you recall, the photon trial is a phase 3 trial comparing EYLEA HD to EYLEA 2 milligrams. And so EYLEA 2 mg was dose on label, which is 5 monthly loading doses followed by every 8-week dosing. EYLEA HD had 3 monthly loading doses followed by every 12- or 16-week dosing. In this post-hoc analysis, we're looking specifically at patients who met criteria for shortening at weeks 16 through 48, and we're asking the question, "How do these patients do at the matched dosing interval at week 12?" So week 12 was a unique time where all the patients had received 3 doses, and 4 weeks later, we can compare vision and anatomy. And so, looking at that population that required or more injections, shortening of their interval, how did they do? It turns out that at baseline, very similar visual acuities. We saw thicker retinas in those patients who required shortening at baseline, and we see that patients at week 12 who required shortening in the HD group had drier retinas in their counterparts, who hypothetically would have required shortening in the 2 mg group. The visual acuity was similar. All in all, this post-hoc analysis tells us that in patients who have a higher need for treatment, we can do better with EYLEA HD at this interval: week 12. In fact, there was a faster time to drying also, and we look at the Kaplan Meier median time to central thickness less than 300 microns; this occurred sooner in HD patients in this harder-to-treat population.

We've had HD in our hands for over a year now, and I think we're learning more and more about who the most appropriate patients for this drug are. In general, me-to-all-comers, really could benefit from HD. You can see faster time for drying, dryer retinas. And so I think that, in general, you know, having second-generation anti-VEGFs is really a come-up for retina. In particular, if we look at patients, though, that have the higher demand, those patients seem to do better with HD than their counterparts with 2 milligrams.

Mark Barakat, MD:

My name is Mark Barakat from Retina Macula Institute of Arizona, and I'm here at ARVO 2025 to present findings from the PHOTON trial. It's actually looking at the baseline characteristics of those patients that were on the 8 mg, so the high-dose aflibercept, in terms of whether they're shortened, extended, or maintained at their intervals. As you all know this is for DME patients that were assigned to either 12-week or the 16-week interval. And some were shortened. It turns out it was 17% or less. Most were maintained or extended. All of them actually really benefit in terms of vision and CST. And then the question was, well, if you look at the baseline characteristics, which one were more likely to be shortened, which one were more likely to be extended? And the short answer is the longer duration of diabetes ahead of time at baseline actually favored extension and maintenance in terms of the CST. So if you had worse CST to begin with, you're more likely to be shortened, less likely to be extended. So in short, all of those subjects actually did really well throughout the trial, regardless of whether they're shortened, maintained, or extended. That 17% or less of those patients were, in fact, shortened, and that it turns out to be a duration of diabetes and the CST going into the trial.

Another pearl that we got from this analysis, if you're looking at the vision going into it. If the vision was 63 letters, that was sort of the threshold for those patients that were—if it was less than 63 letters, they were more likely to be shortened. And in terms of the CST, the cutoff was about 427 microns or so, so in that sense, if the CST was worse than that, again, more likely to be shortened. But ultimately, in the clinical setting, we do what's best for the patients; we just have to be a little bit more flexible. It just gives us the peace of mind to know that not many patients, in fact, needed to be shortened, and those patients that were shortened were still only shortened to the 8-week duration, so still pretty, pretty long durability.

I mean, ultimately, it's a conversation with the patient, right? And I think it begins with keeping them informed and also letting them know this is what the OCT looks like. This is a nice biomarker. This kind of tells us what you're doing. In addition to the vision, and then again, just having flexibility. Yes, I think the vast preference amongst all of us is treat and extend. And I think treat and extend still fits well within this paradigm. This, of course, was a clinical trial setting where things were much more rigorous, more rigid in some ways as well. But yeah, I think it's adaptable.