William Freeman, MD: Brimonidine as a Treatment for Geographic Atrophy


William Freeman, MD, discusses the results of a study he led and other potential treatments for geographic atrophy from a session he hosted at ARVO 2019.

Finding an effective treatment for geographic atrophy was the focus of a number of studies presented at the 2019 Annual Meeting of the Association for Research in Vision and Ophthalmology. William Freeman, MD, distinguished professor at UC San Diego and director of the Jaconbs Retina Center at the Shiley Institute, presented information on a phase 2 study exploring brimonidine as a treatment and also chaired a session exmaining other possible treatments.

Freeman sat down with MD Magazine® to discuss the findings of the study he led and other potential novel treatments that came from the session he chaired.

MD Mag: What is the potential for brimonidine as a novel treatment for geographic atrophy?

Freeman: So, brimonidine is Allergan’s drug, it was initially developed as a glaucoma drug, it has been approved for a long time and there's evidence that, in addition to lowering eye pressure by several mechanisms, it may be a neuro protectant. So, that's important because in glaucoma you want to lower the eye pressure because the pressure is damaging the tissue but, if you can protect the neurologic tissue in the back of the eye that would help as well. So, there have been studies suggesting that it does that. It's not, I think, really proven, Allergan believes it does, and the levels achieved in the back of the eye probably not enough to get neuroprotection to the retinal pigment cells — which are what die in geographic atrophy.

So, what they did is they use their drug delivery system, which is a polymer, that's injected in the eye through a tube and the polymer floats around in the vitreous and releases drug. There's a lot of experience with it with steroids — that product is called Ozurdex. So, they took the same polymer they loaded it with their drug brimonidine. They had to change some parameters and they figured out that they could get enough brimonidine into the polymer to deliver drug to the photoreceptors and pigment layer for approximately three months, after which it's repeated.

So, there have been a series of phase 2 studies which show that the progression of the geographic atrophy, which is the non-seeing area in the retina, is slowed down by this product and probably due to neuro protection where they like to call it neuro protection, because the pigment layer is not really neurologic tissue, it's an epithelial layer and it seems to be real. So, this date has been presented, I presented it, there's many ways to analyze this. Some people like to look at the area, so is the circle of dead tissue enlarging? Some people like to change it to the radius, some people like to do square root transformations. However you do it, it looks like there's something there and so Allergan is proceeding to a phase 3, very large study to test their best formulation of this in geographic atrophy.

MD Mag: In the future, do you expect to see brimonidine used as a treatment method?

Freeman: Well that depends on whether it works. So, there are other companies looking at geographic atrophy and, in the session that I helped chair, there were also studies from individual investigators looking at drugs that are being used for other things to see if they would do anything. It's not clear how promising that is. Allergan spent a lot of time and money doing this, I think they're doing it because they think it will work. The other drugs have to be injected every month or every other month. So, at least with this it's only 4 times a year. So, that's a potential plus but I think the real issue is that when a patient when you can see dead retina enlarging both the doctor and the patient will probably do whatever it takes but you do need that patient compliance. So, there's a concern that in the real world, can you do this 12 times a year forever in an elderly population. I think delivery would be better and they're doing this with this Ozurdex type implant — the Ozurdex is the steroid loaded implant. The other thing they've done is they've made it smaller. So, the Ozurdex, which all retina specialists are familiar with, is a 22-gauge needle loaded with this polymer that's injected into the vitreous. Now, it's down to 25-gauge so that's a lot smaller and the patients will still see some floaters that thing is still floating around in there but, if it really will prevent vision loss, and this is a very bad disease there is really no treatment, I think this will be a big plus.

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