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Pegcetacoplan, an investigational complement factor inhibitor that has the potential to be the first FDA–approved treatment for geographic atrophy in dry age-related macular degeneration (AMD), reduced growth in geographic lesions in the retina after 2 years of treatment. The results, from two phase III clinical trials, were presented at the American Academy of Ophthalmology (AAO) meeting.

In this exclusive 番茄社区 video, , a board-certified medical and surgical retina specialist and ophthalmologist with Retina Consultants of Texas in the Houston area, discusses the data from the DERBY and OAKS trials.

Following is a transcript of his remarks:

The new and exciting data that we're presenting is looking at the 2-year outcomes of a global phase III program involving over 1,200 patients looking at a treatment for geographic atrophy.

So let me back up. So, age-related macular degeneration, AMD, is the most common cause of blindness in our country and in many countries around the world. There's two ways that people lose vision and go blind from macular degeneration. One is a wet kind and one's a dry kind. The wet form of macular degeneration is called neovascular AMD, where patients get abnormal blood vessels that grow in the back of the eye. And we have outstanding treatments for that. We have multiple drugs that are given by direct injections into the eye, and we've been using them for almost 20 years now, and they're highly effective.

The other way that patients go blind, though, there's no treatment for. And that's called the dry advanced form or geographic atrophy. There's no treatment for that. Many patients go blind from that.

You can have both of these forms in the same eye. So the same patient can have wet and dry advanced AMD in the same eye, which makes the conversations a little complicated with patients. Very important from a pathophysiologic perspective. And again, we have no treatment currently for the dry advanced kind of geographic atrophy.

So there's literally dozens of drugs being studied to treat this and the one that may be approved first -- there's no approved therapy now -- but there is a drug called pegcetacoplan, which has a PDUFA date with the FDA of the end of November -- November 26 -- meaning that they're going to report by November 26 if it's FDA approved, which would be a huge milestone in this space as a potential treatment for geographic atrophy. That's the background.

So the data though, is 2-year data looking at the phase III program, 1,200 patients, again randomized equally. A third of them got nothing, got sham injections because again, we have no treatment for this. And two-thirds got the active drug. One-third got every month shots, and then one-third got every other month shots. And then the data, the output, there's three points I'd like to make.

One is an efficacy signal. So through 2 years, the treatment effect of the drug was similar between the trials, with reductions between 18 to 22%. So really on average with monthly or every other month dosing, if you combine them, you get about 20% reduction in the growth of the dead areas of retina called geographic atrophy. So you're getting a meaningful, a clinically meaningful reduction in the growth of geographic atrophy.

It's not 90% reduction, it's 20%. So it's not what patients or physicians or sponsors would like, but it's a step in the right direction, quite clinically meaningful.

Second point from an efficacy perspective is the treatment benefit appears to be increasing over time. So the longer you treat these patients, they seem to be getting more of a benefit from the drug. And there's a lot of fascinating biological potential explanations for that that are being explored.

The second of three points is a safety point. The major safety finding of interest here is that in patients being treated, about 10% of them, if you average all the arms are developing wet AMD. Remember, there's two forms of advanced AMD, there's the dry and the wet kind. We're treating the dry kind. And in treating it, it looks like about 10% of these eyes are developing wet AMD also. Just important to know clinically, when and if we're treating patients with this drug in the real world; we gotta be aware of that potential side effect so that we can then treat the eyes for wet AMD also.

And then the third point is functional. So far everything I've talked about is a benefit on anatomy, but the real question is, are patients gonna see better? And the short answer is this drug does not reverse geographic atrophy. So probably in the long run, the earlier we start treating the patients, the better. So if you have a really small lesions, those are the ones you may be able to dramatically change the natural course and preserve more vision long term.

But the data that we're presenting, all of the prespecified endpoints on function, did not show a benefit with the drug. And probably the reason for that is twofold. One is most of the eyes were enrolling in the trial have very large areas of atrophy already. And secondly, our instruments to assess visual function are not as precise as our anatomic instruments to measure lesion growth.

So when you take our most precise and accurate assessment of visual function called microperimetry -- which is where you look at little spots for visual response inside the macula, in fact the back of the eye, the back 20 degrees of the eye encompassing all the macula -- and you do a per lesional analysis, meaning you're looking just at spots around the area of geographic atrophy, you do see a signal of functional preservation with pegcetacoplan treatment. So it's really the first time ever that we're seeing a direct structure function relationship in the context of active treatment, preserving visual function with a treatment.

So it's exciting, it's an exciting time. Again, the drug is not FDA approved. The FDA is going to comment by the end of November. So my hope is that in the near future, we will have a treatment for this disease that causes a tremendous amount of blindness and has no treatment option today.

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