New Therapies for Geographic Atrophy

Veeral Sheth, MD, MBA: We've had thankfully, 2 new drugs approved for geographic atrophy. This is after having nothing clinically available for these patients who suffer from geographic atrophy. Back in February of 2023, we had SYFOVRE approved, and that came from two studies, the DERBY and OAKS studies, which I can talk about in a second. Then, more recently, in August of 2023, we had IZERVAY approved, again, for patients with geographic atrophy. And that was FDA-approved after two positive clinical trials, the GATHER1 and GATHER2 studies. They’re similar but slightly different, right? They both attack the complement pathway. We know that the complement pathway is kind of a natural pathway that we have in our bodies, it can help fight bacterial infections, and things like that. It's kind of an immune response.

But, we also know that there's this genetic tendency for patients to to have an overactive complement pathway. And that can lead to kind of uncontrolled inflammatory reactions, especially in the retinal pigment epithelium. When you look at some of these patients, or you take, for example, some of their tissue and you look at that tissue under a microscope, what you can see is high levels of things like C3 and C5, which are kind of towards the end of that complement pathway. As we started to identify those as potential targets in the retina, we obviously started looking at therapeutics that could potentially block some of those pathways. The first drug that we had approved, SYFOVRE, looks to inhibit the C3 pathway or the C3 molecule and that will help kind of lower the inflammatory damage being done in the RPE cells and photoreceptors. And then IZERVAY targets just slightly downstream of that, which is the C5 pathway. Again, they're similar in that they're both addressing kind of this complement inhibition, but they're different enough that they're actually targeting different parts of the pathway.

What does that mean clinically? They both have had studies that show slowing down of the damage that's done with GA, in other words, they've slowed down the spread of those geographic atrophy lesions to the order of between 20-30% depending on which study you're looking at. And there's a little bit of a range in the studies. And so from a therapeutic standpoint, we're not talking about stopping the disease dead in its tracks. And we're certainly not talking about reversing the disease. But what we are talking about for the first time is at least having some impact and slowing down the rate of damage that's being done in that patient's retina. And that's something that we are very clear with patients about because a lot of times, even if you start treatment, six months later, a year later, they may notice that, hey, my vision is still getting a little worse. And again, we kind of reiterate that, at least not yet, we don't have anything that will stop that disease dead in its tracks. But we do have these two treatments that can slow things down.