Dr Eleonora Lad: Early Intervention for Geographic Atrophy Prevents Too Much Irreversible Damage

The first FDA-approved therapy for geographic atrophy, pegcetacoplan, slows disease progression but does not reverse it, which means providers need to intervene early before there is too much irreversible damage, explained Eleonora Lad, MD, PhD, associate professor of ophthalmology, Duke University.

Pegcetacoplan was approved by the FDA on February 17. Lad presented the 2-year results of pegcetacoplan from the DERBY and OAKS trials at the Angiogenesis, Exudation, and Degeneration 2023 meeting.

Transcript

Pegcetacoplan for geographic atrophy is slowing progression, not reversing damage. What is the importance of early intervention and what challenges are there?

The main challenge is that geographic atrophy is tough. It's a progressive, irreversible disease that's lifelong. It's also quite heterogeneous. As clinicians, I feel strongly that we need to intervene before too much irreversible damage takes place, especially to the foveal center responsible for central vision.

In retina: location, location, location. The foveal is the most important. It gives us the ability to see faces, tell time, do a lot of our ADLs [activities of daily living]. Once the retinal cells have died off due to atrophy, this is an irreversible process, and it takes away the opportunity to intervene unless you apply regenerative therapies. So, we need to intervene early.

Every other month dosing offers important flexibility for patients earlier in the disease when where they feel that they're still doing pretty well and monthly injections will constitute too much of a treatment burden. So, they would prefer fewer injections, they can start with every other month. When we feel like the disease encroaches on the foveal center critical areas that give them the ability to have good vision and perform all the activities they enjoy, then we can maybe step it up to monthly.

Are there challenges around accurate, early diagnosis in order for there to be treatment for geographic atrophy?

I don't believe so, but we have to start imaging and become better and more sophisticated and more proactive and obtaining images. Autofluorescence is key. Some of us use the infrared that comes with OCT, that's a good surrogate, but ideally autofluorescence, because you can look also at the pattern surrounding the lesions and make a prediction qualitatively for the patient: who will be a fast versus slow progressor or intermediate. We will have to start imaging, get really comfortable with image interpretation, do it frequently now to get ready for this. So, we can really identify the patients that are in highest need and start early intervention. Robyn Guymer, MBBS, PhD, of the University of Melbourne] did a beautiful job with an editorial recently on this topic.