ARVO LIVE: YOSEMITE and RHINE trials comparing faricimab to aflibercept

Ophthalmology Times® talked with Roger Goldberg, MD, MBA, about macular leakage area in the YOSEMITE and RHINE trials comparing faricimab to aflibercept at this year's ARVO meeting.

Video transcript

Editor’s note: Transcript lightly edited for clarity.

Roger Goldberg, MD, MBA:

Hi, I'm Dr. Roger Goldberg from Bay Area Retina Associates, and it's great to be here at ARVO 2023 in New Orleans. I gave a talk at this meeting looking at macular leakage area in the YOSEMITE and RHINE trials comparing faricimab to aflibercept.

What we saw overall was that faricimab during the head-to-head phase did better job at reducing macular leakage versus aflibercept, with a greater reduction in the average amount of macular leakage after 4 loading doses, and similarly, a shift in patients who had a lot of leakage down to an increased proportion of patients with absence of macular leakage after 4 loading doses.

So what we did is we took all the patients from the YOSEMITE and RHINE trials but the aflibercept and faricimab treated eyes, and we looked at how much macular leakage they had after the 4 loading doses.

Again, this is a true head-to-head comparison of these two drugs in diabetic macular edema, and we broke the group's up into quartiles. Quartile 1 had basically resolution of macular leakage less than 1 square millimeter of macular leakage.

The fourth quartile group had greater than 10 millimeters of macular leakage after 16 weeks of treatment. Now, we looked at first of all, does macular leakage matter, and does resolution or impact on macular leakage have an effect? It certainly does.

First of all, patients who had persistent macular leakage in that fourth quartile group, they tended to be younger, Hispanic, and they tended to have worse vision, worse CST on a worst diabetic retinopathy severity score at baseline. And then, what we do is we follow those patients out over the first year. It turns out that patients who have a resolution of their macular leakage after the loading phase, well they tend to have better visual acuity after one year on therapy. They tend to have thinner, drier OCTs and a greater proportion of those patients have absence of intraretinal fluid at one year.

We then look more specifically comparing aflibercept versus faricimab just over those 4, during the head-to-head phase when they both out for loading doses.

First of all, at baseline, the groups were very well balanced with about 25 square millimeters of macular leakage at baseline with very similar distributions at baseline, and what we see very clearly is that the faricimab treated eyes have a much greater shift to the left in terms of reduction in their macular leakage.

So, if we look at the proportion of patients in that quartile 1 group who have very little or no macular leakage, and we see that nearly doubles in the faricimab treated population versus the aflibercept arm. Similarly, if you look at the proportion of patients who have still quite significant macular leakage more than 10 square millimeters, we see almost double the number of patients in the aflibercept treated arm versus the faricimab treated arms. So we're clearly seeing a shift from greater leakage to reduction in macular leakage with faricimab versus aflibercept.

Now, of course, the key question is, well, what might be driving that reduction in macular leakage? And, it's interesting, we see from other studies including the RUBY study, which looked at comparing aflibercept in addition to an angiopoietin-2 inhibitor, we saw overall, no difference in central retinal thickness and the READ-3 study, which looked at quadruple the dose of Ranibizumab there is no difference in central retinal thickness, but what about macular leakage itself? And here, actually, the best data comes from the PHOTON study which compared 2 milligram aflibercept versus 8 milligram aflibercept, and at the head-to-head phase after 3 loading doses in that study, there is no difference in the reduction of macular leakage between regular dose aflibercept and high dose of aflibercept.

So, it really points to the effect of angiopoietin-2 inhibition, particularly in macular leakage, and that might be the key biomarker here to really point to the efficacy of angiopoietin-2 inhibition, in addition to VEGF-A inhibition.