An expert panel discusses the role of complement C3 vs C5 therapies and provides guidance for treatment selection in geographic atrophy.
Jayanth Sridhar, MD: Like you said, it’s great to have more than one option, it’s always better to have more options. With more options comes more complexity and decision-making, and I think the question we all have, and I’m still thinking about this, is if both of these end up as options for us, how do we make treatment decisions given that we have such different trial data in terms of extrafoveal lesions versus subfoveal? Monthly versus every other monthly. How do you think we’re going to differentiate that as a community when we start deciding, do we use this drug or the other drug? Do you think the mechanism matters in terms of where in the complement system we target?
Eleonora M. Lad, MD, PhD: It’s interesting you raise that, and maybe I’ll pitch this over to David, but the theory about attacking C5 is that you might leave some of the complement system intact because we have complement for a reason, and so you’re not shutting down the whole system. David, do you think there’s a big difference between C3 and C5?
David R. Lally, MD: I think we have a lot to learn. We’re still in the early stages of exploring and investigating the role of using these 2 tools in our tool basket. The overwhelming theme I see is that they both appear to have an effect. I don’t in my head look at all the little percentages because they can vary among the trials, even in the individual drug that’s being studied. That speaks to the different patient populations in these studies. Like DERBY, in GATHER2 there were more ex-US sites that were involved. Maybe there are genetics that are involved that affect their response. I think they will both be helpful to our community, but I think it’s too early to say whether I’m going to do this one or that one. A lot of it’s going to depend on other factors as well. Coverage factors and real-world experience are going to be critical. How will the safety be in the real world? We know with another product in another disease that was approved a couple of years ago that the real-world safety was different than what we saw in the clinical trials. I see a role for both in my practice, and I think the real-world experience that I have with them will dictate what happens going forward.
Jayanth Sridhar, MD: The great thing about multiple options is that not all our patients are going to respond equally to both, we’ve learned that from wet macular degeneration and other conditions we inject for. We have the luxury of multiple options. We have trial data that show similar percentages, but it’s not the same percentage of patients responding to each one. We have some patients who respond better to one drug than the other, so to our question of monitoring early, it’s not just for safety, but we must have good, convenient, accurate, and maybe automated ways of measuring lesion regression over time. These trials had the benefits of big reading centers and things that were designed to capture that lesion progression over time. We don’t all have that in our individual practices, but we may have to measure that because if a patient is not meeting the percentages we saw in a trial, down the line if both drugs are there, and if we take away payer issues, maybe you have the option to switch. How are we going to make that decision? The most logical thing would be if a patient’s not responding the way they should be, according to trial data, then maybe this is someone who’s not responding within this group, and they should be tried with the other drug to try a slightly different mechanism. Having a way of capturing our progression over time in an easy, fast, and accurate manner will be helpful. If we have models, thinking ahead, that could model what it should have been like based on trial data, that’d be helpful to make a decision tree.
Eleonora M. Lad, MD. PhD: How about your patient selection where you’re thinking about these 2 phase 3 programs? How would you select? Who would you treat first and who would you treat last? How would you tailor your drug choices in the beginning, aside from follow-up? Nancy?
Nancy M. Holekamp, MD, FASRS: It’s important first to have FDA approval, then to see what the FDA label says. Then have a discussion with patients who meet the label, and the label is based on clinical trial design, so I’m not quite sure what the label will be for each of the programs. Small differences come to mind, and it’s very difficult to compare across clinical trial programs. But perhaps if I have someone who has CNV [choroidal neovascularization] in one eye and GA [geographic atrophy] in the other eye, I know that they’re already at higher risk for choroidal neovascularization. I might choose a drug that in the clinical trials had the lower rate of CNV conversion. However, on the other hand, it may not be possible for someone to come in monthly, if one of the drugs is only getting a label for monthly. In that case, I would choose the other drug. I think we all have preference that we try to tailor to individual patients.
Transcript edited for clarity