VIDEO: Recent advancements in AMD treatment

Editor’s note: This is a previously posted video, and the below is an automatically generated transcript to be used for informational purposes. Please notify hliptak@healio.com if there are concerns regarding accuracy of the transcription.

In terms of the new treatments for macular degeneration, it's an exciting time for macular degeneration because we have a lot of new and innovative treatments that have come out. And as most of you may know, macular degeneration is a disease that has sort of an advanced form. And the advanced form takes two parts. There's the wet macular degeneration component of disease, for which we've had, you know, treatments for a while. And then there's the dry form of the disease, which in particular we refer to as geographic atrophy when we're talking about advanced disease. So let's start with the wet macular degeneration landscape. You know, we've had treatments for quite a while, and most of the treatments that we currently use are what we call anti-VEGF drugs. These are medications that are in injected in the eye and help to stop new blood vessel growth, which is at the core of what wet macular degeneration represents. And so in the last couple years, we've had some pretty, you know, interesting and new therapeutics come online. So I'll start in order of time. Basically the first sort of newer treatment for wet macular degeneration that came about is a treatment called Susvimo, and Susvimo essentially is a port delivery system for wet macular degeneration. So this therapy is actually a complete paradigm shift in how we treat the disease. So in this particular therapy, there's actually a surgical component to it. So patients are taken to the operating room, where a port is implanted with drug, and that port then releases drug over a six-month period. That port can then be refilled, and that saves patients the burden of intravitreal injections, which in general can be anywhere from one to maybe three months. In fact, you know, most of the time when I'm counseling a patient with wet macular degeneration, I'll explain that, you know, we have therapies, these anti-VEGF drugs that we use, and they will probably be given every one to three months or so, based on their treatment response. And so Susvimo got FDA approval in October of 2021 and came on the market and has been out since then. Essentially, the drug, when it was compared to monthly Lucentis, showed non-inferiority with an every six-month refill. So this gives patients an option, then, albeit a surgical option, to have a disease treatment that is much different than our current regimens. And so the port delivery system or the Susvimo treatment basically got a one-year start and then in October of 2022, so essentially one year later, Genentech did voluntarily recall Susvimo because they had some concerns about the quality control on some of the implants. There's essentially an issue with the commercial supply that the implants didn't really live up to the company's standards, and so they did voluntary recall. So there's been suspension of the Susvimo implants since that recall. So while it did get out for about a year, currently that treatment would not be available to newer patients. Any patients that did have the port implanted can have the refills done in the office. So that therapy does continue for patients that did receive the port implant. But new port implants are not being placed currently at this time. Following up on that, a drug that did receive FDA approval later was Vabysmo. And Vabysmo essentially is faricimab. And this drug is an engineered bispecific protein that binds both VEGFA and angiopoietin-2. And so both Ang-2 and VEGF are key drivers of angiogenesis. They drive angiogenesis, they drive inflammation, they drive vascular instability and leakage, all of the things that are, again, sort of at the core of what the damaging effects of wet macular degeneration are. And so faricimab was the first bispecific antibody designed to block both of these molecules. And essentially, the novel component to this drug and sort of the interesting part of it and why it's become incorporated in a lot of therapy is that the durability of the drug. So the drug was studied for wet macular degeneration in two large studies, Tenaya and Lucerne. And in these studies, the drug was compared to aflibercept or Eylea, and aflibercept was given at a loading dose of once every four weeks times three doses, and then from that point forward was given every eight weeks. And that was compared against Vabysmo or faricimab, which was also given in a loading dose every four weeks for four doses, and then ultimately given in a dose range of up to every 16 weeks. And so basically at the end of the trial, it was a non-inferiority trial, and Vabysmo was not inferior to Eylea. And the interesting part about that trial was the design of the durability of the drug. So Vabysmo was dosed up to every 16 weeks. And when you took the patients as a whole, about 45% of patients were able to go up to every 16 week dosing with Vabysmo. About a third, or 33% of those patients, received drug every 12 weeks. And then about 22% of patients were able to go every eight weeks. So when you take the patients as a whole, up to 78% of those patients were able to go every 12 weeks or more with Vabysmo versus, you know, the every eight week dosing of aflibercept. And again, that was a non-inferiority study. So again, the interesting and exciting part of that is this gives us another option to treat patients and hopefully will give us a bit more durability in treating patients so that we can go past, you know, these, you know, every one to three-month treatment regimens that we currently have for our patients. In terms of the treatment options for dry macular degeneration, we really haven't had any treatment for dry macular degeneration for a very long time. And so it's very exciting, and this is very recent news, that the FDA approved a new drug in February of 2023. And that drug is Syfovre, which is pegcetacoplan. So pegcetacoplan is a new drug and represents the first and only treatment for geographic atrophy secondary to age-related macular degeneration. And this is a very important new development because this drug is treating an unmet need in macular degeneration. And we know that over a million people in the USA lose vision from geographic atrophy, up to 5 million people worldwide. So it's a huge unmet need. And this FDA approval is based on the phase three studies of the OAKS and DERBY trials, which were two-year studies, and they looked at how this drug impacts patients that have geographic atrophy and what exactly can be done with that. So the study essentially looked at patients with geographic atrophy, and it basically reduced the progression of geographic atrophy by basically 20 to 30% over that two-year period. So this is a huge, a huge step forward in our therapeutic options for our patients because again, currently we have no treatment, and now this gives us something that we can actually, you know, use with our patients. So it's a huge step forward for us to have this. Now, the important parts to know about this in terms of what we discuss with our patients, it is a novel therapy. It is a little bit of an interesting treatment because there really are no parameters around how we use this. And what I mean by that is normally when we treat patients with wet macular degeneration, we're kinda monitoring their impact and we can see, you know, biomarkers on OCT, and clinically, that will give us an indication of how the treatment is working and whether we need to change treatment. This treatment is essentially a fixed treatment, and basically it's given every month or every other month, and patients are given this treatment on a set treatment pattern. So there, again, there is no modifications made based on response. And so this new treatment paradigm, again, for us because we're used to following OCTs and things like that to see results in this treatment regimen, essentially patients are coming in, if they are being treated, they are being treated on a fixed interval dose. You know, we talk about the efficacy, like we mentioned, the every other month treatment regimens seem to show about a 16 to 18% reduction in the growth of the geographic atrophy lesions, whereas the monthly were a little bit higher, 19 to 22% response rate to that. There does appear to be, when you look at the graphs, over time, there does appear to be an improved treatment effect over time, so that essentially, when you look at even the last six months of treatment for these patients, there's a separation of those curves of the treatment versus the non-treatment groups. So that's where you kinda get up to this maybe 30% reduction in lesion growth, when you're looking at like the last six months of data. It's exciting because it may translate into increased efficacy with duration. And there are definitely some questions being asked, you know, to understand why that might be with that drug. So anyway, exciting news, exciting things to see, you know, for our patients that we haven't had before. When you're talking about these trials, you know, you always wanna look at the safety aside from, you know, what the drugs can do for our patients, you know, what are the things that we need to be aware of? We had, you know, some signals early on in some of the Philly trials, which are the phase two trials for this drug, that there may be some increased incidences of wet or exudative AMD with these drugs. And in fact, when you look at the monthly, every other monthly and sham, you talk about a risk of wet AMD of 12%, 7% and 3% in that order. So there does appear to be that pegcetacoplan can induce some wet macro degeneration in patients receiving it, and it is somewhat dose dependent there. So, you know, we need to monitor our patients when we're treating with this drug. But it is also important to know that in the study, the patients that did have these exudative changes, they were treated at the investigator discretion. So these patients were then treated with our, you know, standard drugs for wet or exudative AMD. And in patients that did receive treatment for the wet AMD, when they were given treatment, they did seem to perform similar to the patients that did not develop wet AMD. So this suggests that we really may be able to treat these two manifestations concurrently in the same eye, and maybe that, you know, is a positive thing for our patients. So if they do develop that, because we all have patients that have both forms of the disease, right? So even without, you know, these treatments, patients with dry macular degeneration will develop wet, and our patients who are receiving treatment for wet macular degeneration, many of those will lose vision to dry macular degenerative changes. So having a treatment for both does give our patients some options. You know, obviously, the other things that we're very, you know, keen on being aware of are, you know, the rates of infection with these drugs. And the good news about pegcetacoplan treatments for our patient with dry macular degeneration is the intravitreal injection rates, they had similar infection rates to our patients that get wet macular degeneration rates. So I think in the studies, that ended up being somewhere around 0.034%, which, again, is comparable to the anti-VEGF treatment trials that we have. The other important piece that we've spent a lot of attention on these days is inflammation because inflammation with any new therapeutics is something that we need to pay attention to. In the trials, when you look back at the data collated, you do find that there are some inflammation rates that did show up with pegcetacoplan. So in the patients receiving monthly, it was around 3.8% of patients did develop some degree of inflammation, along with 2.2% of the every other month groups and 0.2% of the sham groups, so again, showing a dose-dependent signal for inflammation. But it is very important to note when you look at this data that some of these patients were coming back from the data that originated in 2018. And in these clinical trials, it's important to know that the drug when it first came out in 2018, there was a signal for inflammation, and the trial was initially stopped because of this inflammatory signal that was seen. And so the patients that were receiving the product, they basically went back, the company did, after they stopped the program, and they reformulate the drug. And then that was reissued in 2019. So again, those higher incidents of inflammation, some of those represent those early cases, and the inflammation drop did precipitously drop after that. And you know, again, in context, it's important to note that the inflammation that we'll see in these patients tend to be anterior uveitis, maybe with some vitreous cell or iritis. And we weren't seeing the cases of retinal vasculitis that we have seen with some of the other therapeutics that have really gotten a lot of attention recently. So again, that's a hopeful and optimistic look at some of the inflammation there. But it's very important to be aware of because we're all concerned about those things when there are new therapeutics being introduced.