Dr Coney expands on the role and impact of approved label dosing of faricimab.
Jim Kenney, RPh, MBA: Dr Coney, what has been your experience in the real-world setting with faricimab? Does the approved label-dosing interval make sense in your patient population?
Joseph Coney, MD, FASRS, FACS: There are 2 ways to look at this. My early utilization of faricimab has been in treatment-experienced eyes. For those individuals who have been treated with a number of injections—most of them for a number of years—they’ve always had some type of fluid, either fluctuating fluid or recurrent fluid, particularly when I try to extend them out. Those individuals have done extremely well. I’ve been able to extend them an additional 2 or even 4 weeks. We’re still in the early adoption phase of this drug, so I don’t have any long-term data more than 6 to 9 months. But the majority of those eyes are doing fairly well with less treatment burden.
Individuals I’d transitioned to early utilization in naïve eyes are doing extremely well. The dilemma for me was trying to get comfortable with whether I followed the on-label dosing that was in the clinical trials, which was after their loading dose. Do I extend them a month at a time? Every 2 weeks is what I normally do with a lot of my patients. For individuals whom I’d treated early on, who’d had that rapid response that was completely dry, I had a discussion with them. I let them know that historically I would probably want to go 2 weeks, but if they wanted to go to a whole month, I was OK with that. I’m seeing some of those patients back 1 month later after the loading dose, and they’re doing fairly well. I’m getting more comfortable with those individuals because they had very similar responses to what I saw in clinical trials.
There’s something interesting about treatment-naïve patients. I still don’t feel comfortable extending those patients. Clearly, I had to back down on some of those patients. My patients with diabetes had a little more returning fluid than my patients with AMD [age-related macular degeneration], so I’m still trying to figure out how to address some of these individuals. I don’t go back to a monthly loading dose. I tend to start my loading dose once [a patient] recurs. I bring my loading dose back to where the fluid recurred and then do 3 or 4 injections there before I try to reextend them. That’s my mindset.
Over the next year, my colleagues and I will have a better understanding of how to use this in individuals with treatment-naïve eyes to those highfliers. My thought is that there’s something that may be special about Ang2, but we have to let that molecule build up. That’s where that loading dose, as we saw in clinical trials, had the more efficacious robust response. Early on, extending those patients from the initial therapy may not have been the best thing, and I may have acted too fast. I’m trying to see if I left that molecule build up a little, then maybe I can get that increased durability that I’m hoping to see.
Jim Kenney, RPh, MBA: Dr Luo, can you share your experience?
Caesar Luo, MD, FASRS, FACS: I completely agree with you, Dr Coney. The blockade of Ang2 is acting on something called TIE2. It’s a switch, and it’s something that turns the eye toward vascular stability, compared with Ang1, which is a protective molecule in the eye. So I agree; it’s a switch. It’s not like the blockade of VEGF, which is just trying to sop up as much of this cytokine as possible. It takes a little time for that to work. That’s a great point. I also agree with you that there’s been a little difference between my patients with wet AMD and DME [diabetic macular edema]. At this juncture, I was doing mostly highfliers, patients who’d had a very high treatment burden and who were looking for something a little different. A lot of times, in patients with DME, it’s very different. It’s not primarily VEGF-driven, as we see with macular degeneration. But they tend to be more inflammatory at that point, and you’re not addressing enough of that no matter what VEGF or Ang2 molecule you’re using. My patients with DME haven’t had the wow effect, but I agree. [About] 40% of my patients have had a lengthening of their treatment interval. It’s not everyone, but it’s a very large number. If I tell my patients sitting in the chair that I’ve added even an extra week to their treatment cycle, from 4 to 5, they’re extremely happy. It’s a great feeling to be able to tell patients that you’re out 2 weeks longer, because they’ve been having a lot of difficulty getting in.
I like to separate my buckets a little. When we think about [patients with] wet macular degeneration, there are the nonresponders, the suboptimal responders, and the hyper-responders, the ones who are very responsive to anti-VEGF. I’ll try faricimab on all these patients. The ones who are very responsive at every-4-week dosing and swell at 1 extra week are great patients, so we can add extra time. But even for the suboptimal [responders] and nonresponders, I like to see if adding that Ang2 blockade helps them with more drying effects. That’s what we saw in the phase 3 clinical trials. It’s a good option for a large number of patients, and I’d rather try them to see if that helps. If it works, it can work very well.
Jim Kenney, RPh, MBA: Dr Sheth, what’s your experience with faricimab?
Veeral Sheth, MD, MBA, FACS, FASRS: I agree with the other 2 doctors’ comments. I’ll add a couple of things. For most patients I’ve switched to faricimab, I’ve been able to keep at least the same interval, but most have been able to be stretched out. We’re learning a lot. We’ve had this drug in the real world for just under a year, so we’re finally getting the opportunity to see these patients back and tweak their dosing schedule. What I’m noticing is that in a lot of our patients diabetes, there’s not a wow effect but a delayed wow effect. Dr Coney made the point that it takes a little while for this Ang2 component to build up. But once it does, you start to see results in some of these patients that you weren’t getting with anti-VEGF alone. That reinforces this dual mechanism of action being significant for these patients. Many of them are being extended further out than they were with anti-VEGF alone.
Transcript edited for clarity.