Drs Lally and Khanani expand on key takeaways from the GATHER1 and GATHER2 studies.
Ryan Haumschild, PharmD, MS, MBA: Dr Lally, we heard a lot of great information, even consistency among the subgroup analysis and the durability of response over time, which is something that we all, I think, agree upon is really important for these patients. [Do you have] any thoughts around GATHER1 and GATHER2, and [what is] your interpretation of the significance of the end points that were highlighted?
David Lally, MD: I think what I was happy to see with the GATHER1 and GATHER2 studies is that they did meet their prespecified primary end point in both trials. When I think of geographic atrophy [GA], it’s a very heterogeneous disease in my mind, and there are probably a lot of different types of eyes that are in these trials, and I think that’s part of the reason why we see different efficacy results among GATHER1 vs GATHER2 in terms of the percent reduction of growth. Just like we see differences in the percent reductions of growth in DERBY vs OAKS, I think a lot of it is if you ran these studies 10 times, you may likely get 10 different results because of just the heterogeneity of the populations. And in GATHER2 there were more international or global X-US patients that were in the study as opposed to GATHER1. If we look at DERBY and OAKS, there were more patients that were from outside the United States in DERBY vs OAKS. OAKS had more US patients. Does that make a difference in the efficacy? We really don’t know. But for me, it’s not so much about the exact number percent of reduction but it’s showing that it works and that we see the effect increasing over time. In GATHER1, we saw that at 18 months the effect was greater than at month 12. So that’s encouraging. The other thing I really liked about the GATHER1 and GATHER2 studies, as Dr Khanani mentioned, is the safety profile of [avacincaptad pegol], with no signs of inflammation. That’s something as retina specialists we’re always on the lookout for. We’ve had other FDA-approved therapies for other retinal diseases that hit the market where there were issues with inflammation in the real world. So it’s really good to see that inflammation [is] not being seen with this specific molecule. Also, not seeing any signs of ischemic optic neuropathy makes us happy. I think the fact that it met its prespecified primary end point in 2 large pivotal phase 3 studies, along with the really good safety profile, makes it a very encouraging therapeutic that I hope we hear from the FDA, like our shots mentioned soon, and that we have it as another tool in our tool belt to help our patients.
Ryan Haumschild, PharmD, MS, MBA: Dr Khanani, as we start to see these agents become FDA-approved and we start to see them being utilized and commercialized, what role do you think these complement inhibitors may play in the management of GA? Do you see quick uptake? Do you see people utilizing them early on in treatment? Talk us through a little bit of how you start to see the utilization of these new therapies spreading out among providers.
Arshad Khanani, MD: I think, Ryan, we know that obviously for any new treatment to be utilized, we need payer support and coverage. So obviously once we have the coverage, many therapies are available, but they don’t have a J-code or they have a temporary J-code, which is a lot more work and risk for providers. I think as we discussed earlier, neovascular AMD [age-related macular degeneration]is a very acute disease. We need to treat it now or very soon. GA does impact patients for a few years but treating them now vs a few months from now may not make a huge difference. So the first thing is obviously practices need to make sure that they’re getting paid for the drug they’re purchasing. And then the second is I think there’s a lot of education that needs to be done, not just for the patients, but also for the retina specialists in the community who don’t know the data for optometrists, or general ophthalmology colleagues, really showing the benefit of these complement inhibitors. We didn’t see any functional or vision benefit with pegcetacoplan [Syfovre] at 2 years. And many of the colleagues I talked to talk about, well, you are slowing down the GA growth, but you’re not making a functional difference. And my answer to that is that obviously clinical trials enroll a specific type of population, and if I have somebody that I intervene early, they may likely benefit. And differences between agents the unveiling, I can’t wait for the ACP [American College of Physicians] fundus autofluorescence 2-year data on visual acuity to see if there is a benefit. We saw that there was a trend towards stabilization in GATHER1. So we’ll see how physicians treat because we not only treat GA and OCT [optical coherence tomography], but we treat the patients. And I can guarantee you that if you save photoreceptors; you are going to save functional vision. I think the uptake will be slow because of the utilization, because of J-code, and whatnot. And then once we start treating with any new agents, I think many physicians are waiting for the real-world data, as Dr Lally said.
If real-world data shows that we don’t have, let’s say, higher rates of inflammation with pegcetacoplan that’s in the label it’s up to 4%. So we need to see, we don’t have any cases that are advanced in the real world or cases of irreversible vision laws that happened with other agents, then I think the uptake will increase when people will know that, OK, now we have thousands of patients treated, we are not seeing any new safety signals that are rare and there is a risk of ischemic optic neuropathy, but it’s unclear whether it’s related to [the] drug or just the aging. So if we don’t get those signals, then I think the uptake will increase. In my opinion, there are going to be early adapters, like Dr Lally and I, who have been part of the trial and know the drugs very well. But I think for the majority of the community [this] is going to be slow uptake.
Ryan Haumschild, PharmD, MS, MBA: Well, it sounds like a great opportunity for education and maybe if they tune in to this peer exchange, they’ll learn a lot. I know I have [learned] throughout this discussion about some of the pros and cons in the clinical trials, and I think that will help give confidence to our providers that are looking to treat patients with a high unmet need.
Transcript edited for clarity.