Ryan Haumschild, PharmD, MS, MBA: Dr Khanani, we’ve discussed geographic atrophy [GA], and you did a great job giving an overview. But if you could, let’s get a little more detailed in discussing the disease progression. How do you see the disease evolve over time? Dr Lally just spoke about traditionally it was known to be slowly progressive. What are you seeing recently, and what spectrum of vision loss is seen in geographic atrophy that, as we mentioned, will impact patient quality of life and overall vision?

Arshad Khanani, MD: Ryan, I think that’s a really good question because we see these patients month after month, year after year in our clinic. Many of these patients had perfect vision when they started with GA in a nonfoveal, far away location with a small spot. Then you look 5 or 10 years down the road, you see that these patients are legally blind from this disease. What this disease does is that patients lose the ability to perform daily tasks and can progress to legal blindness. This is a disease that progresses 100% of the time in 100% of patients. I don’t think Dr Lally might have any patients where you just have a small GA lesion that stayed the same for a long time. And if that’s the case, that’s not GA, that’s some other dystrophy that’s going on. Of course, the disease, once it grows too large and damages the whole vision, then of course, it slows because there’s not much to lose.

If you look at the number or the percentage of patients who lose their ability to drive, I was surprised personally when I looked at it; 67% of patients will lose their ability to drive in less than 2 years. Then 16% or so will be legally blind in just over 6 years. So, this is not a disease that will be slow enough for you to have your vision for 10 or 20 years. This is, as Dr Lally said, it’s not as fast progressing as nAMD [neovascular age-related macular degeneration], but it’s quite fast progressing. Our hope is that we’re able to slow this so the patients can have better functional vision and independence for a longer period of time. It has been really frustrating as a retina specialist that up until now, we have not had any treatments for it.

Ryan Haumschild, PharmD, MS, MBA: It’s interesting when you talk about that. I think about transportation vulnerability and social determinants of health, and how they stay compliant with their medications and show up on time, seeing that type of progression. As you said, what a high unmet need for this patient population. It’s exciting to see that. I know as a payer, Dr Lopes, that’s something to think about as well, if we’re going to cover a treatment, how do we make sure these patients can receive it, and how do we slow that progression? As a payer, I know we’re also managing a benefit for employers. As employers want to have presenteeism and have their workforce continue to perform, that’s another important consideration. I think the next great question we should probably transition into is, we have a large payer group that tunes into these, and one of the major things we need to understand is, what the distribution of these patients looks like and how prevalent is the disease. Dr Lopes, how common is GA, and what do you think the incidence or prevalence is within the United States?

Maria Lopes, MD, MS: I think Dr Khanani alluded to this before. I think we probably don’t know the real number because up until now, there hasn’t been any treatment, basically AREDS [dietary supplements] and over-the-counter vitamins. The true incidence I’m not sure we know yet. We’ve alluded to that we probably would have somewhere around 1.5 million who have GA, but this number is probably bigger. And over time and as we age, we have an aging demographic population, with 20% of these patients having, I believe, AMD [age-related macular degeneration], So, the number could be much bigger than what we understand it to be today. And it really is about the diagnosis. It’s about the identification of patients so that hopefully they’re initiated on the appropriate treatment early enough that it is going to impact the rate of progression and allow for better function. Also, a significant percentage of these patients have bilateral disease. Imagine not only being affected in 1 eye, but as many as 48% to 65% have bilateral disease, where again, they go legally blind. So, we’re looking at treating potentially both eyes, not just 1 eye. That adds, of course, to the volume and the cost that we’re going to see. But again, I think it starts with education. It starts with the appropriate diagnosis. Now that we have 1 effective treatment and more to follow, there are options for patients.

Ryan Haumschild, PharmD, MS, MBA: Dr Khanani, building upon that, you’ve experienced a lot of exposure to these patients. I’m sure you have a lot of familiarity with what the disease prevalence looks like. But I’m curious, what are some of the typical patient characteristics of someone with GA, regarding age, gender, and race, even comorbidities? I know a lot of patients with metabolic disease sometimes can present. I’m curious if you could describe maybe the type of patients who present with GA.

Arshad Khanani, MD: It’s called age-related macular degeneration, so the older the patient, the higher the risk. The majority of patients in my clinic are in their 70s and 80s, and the rate of having GA increases exponentially in each decade of life. In terms of what are the characteristics, obviously, you have to look at the family history. The genetic profile is important. We have several gene mutations in complement factor H, or eye genes that make people prone to progressive disease. We have gender; most of the patients with GA are female. There are also links to cardiovascular disease. Another social factor is smoking. Smokers have pretty progressive disease, and we hope that when they see us, we try to counsel them to stop smoking. I think sometimes smoking impacts how fast it’s growing. Obesity and poor diet have been implicated in GA. So, being on a Mediterranean diet and eating green leafy vegetables can help. But none of these factors are too modifiable, Ryan, so of course, you can quit smoking, you can have a healthy diet, and you can exercise, but that doesn’t mean that stops the disease. It may slow the progression a little.

Most of the patients who come to our clinic are pretty advanced. As Maria said, we don’t know the right number because many of the patients with very early GA are with the optometrist or the general ophthalmologist because they may be asymptomatic or they’re seeing 20/20, so they’re not referred to us. Sometimes visual acuity itself can fool the referring doctors, “Oh the patient is doing fine. I don’t need to do anything.” What happens is, the atrophy progresses over time and then your vision will go down. So, our job is to catch this early and treat it early so we can have better preservation of the photoreceptors. I think going forward, the population demographics in my clinic are going to change once we have treatments available. Obviously, we have the recent approval of pegcetacoplan. I think what’s going to happen is we are going to see more and more patients at earlier and earlier stages of the disease. But again, it’s an age-related disease, most of the patients are in their 70s, 80s, and 90s.

Ryan Haumschild, PharmD, MS, MBA: Early detection seems like it’s so important here. And if they are going to their general optometrist or ophthalmologist, how do we make sure there’s great screening for this? Because you mentioned earlier that the disease progresses quickly. So, better identification and understanding of some of the risk factors are going to be important.

Transcript edited for clarity.