At Angiogenesis, Dr. David Brown presented the Phase 2 results of the CANDELA study for high dose aflibercept 8 milligram for wet AMD; here, he discusses those results.
At the Angiogenesis, Exudation and Degeneration meeting, David Brown, MD, FACS, presented his talk, “CANDELA: High Dose Aflibercept for Neovascular AMD.” Dr. Brown is the Director of Clinical Research at Retina Consultants of Texas.
David Hutton: I'm David Hutton of Ophthalmology Times, and our team is providing virtual coverage of Bascom Palmer's Angiogenesis conference held in Miami. Joining me today is Dr. David Brown, Director of Research at Retina Consultants of Texas, who will discuss Phase 2 results for high dose aflibercept 8 milligram in wet AMD. Thank you for joining us today, Dr. Brown. Tell us about these exciting results.
Dr. David Brown: Thanks, David. This is the first presentation of the 44-week results of the CANDELA study. And if you go through time, in almost every anti-VEGF trial we've done, we've seen a dose response curve: Half milligram did better than 0.3 in ANCHOR and MARINA, bevacizumab did better than ranibizumab in CAT, higher molar blockade you saw aflibercept did better than ranibizumab and, in the head-to-head trials, more anti-VEGF blockade.
So the big question is, can we do better with a higher dose of what's currently the market leader, aflibercept?
We tested 8 milligrams versus 2 milligrams in 106 patients, 53 patients in each arm. You know, there was some question whether this would make a difference. If you look at the HARBOR data with ranibizumab. There wasn't a difference when you made it four times higher dose. This is a different molecule though aflibercept is bispecific, right? It gets placental growth factor and anti-VEGF; it's also a larger molecule than ranibizumab.
What did we find? We found that in a population that was not a strict monthly, although it wasn't what I call the criminal retreatment criteria of many of the other trials, you had physician discretion on when to treat based on fluid.
It was masked, so it's head-to-head. At every time point, there was better anatomy with 8 milligrams. In other words, you dried up more of the retina. That was statistically significant. If you looked at fluid in the entire macular scan, almost double the amount of dry patients.
And more importantly, we actually saw a visual acuity benefit with this treatment paradigm in this population. 7.9 letters gained with the 8 milligram aflibercept versus 5.7 in the 2 milligram, and these time points were pretty consistent throughout that the higher dose, dried out more retinas, and improved the visual acuity.
It certainly shows us that it's probably a better drug, especially in a population where you're not treating monthly—and that's more real world because things get in the way, right? Christmas, Hanukkah, gallbladders—you miss appointments. And so in the real world, I'm hoping we can get this molecule.
Currently, it's being tested in a Phase 3 DME and AMD. That's a little different. When you do something for registration, you'd have to go against labeling, so it's going against aflibercept load and then every eight weeks, but we'll see. We're doing extended dosing out to 16 weeks, and I think it may be a decent competitor for the new faricimab and upcoming Kodiak molecules.
David Hutton: You mentioned that Phase 3 trials. Really what's the next step for this?
Dr. David Brown: Basically, they're fully recruited. There'll be one-year trials. You know, they'll have to do some more studies to try to get the kind of label that faricimab got, the 4-week to 16-week, but we'll see.
We were concerned about a couple of things. I'm always worried about systemic safety when you're using an anti-VEGF that strong in the eye. We didn't see anything in this trial. We had two patients with increased hypertension. Fortunately, one was 2 milligram and one was 8 milligram, and we saw one patient with mild inflammation in the 8 milligram arm.
You know, as we get bigger, we got to make sure that we're not causing inflammation like a, you know, brolucizumab was a lot of protein in a molecule; this will be certainly more protein. So they're not out of the woods, but it's a promising start.
Note: This transcript has been lightly edited for clarity.