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AAO 2023: Unpacking the diverse approaches in dry AMD research

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Article

Peter K. Kaiser, MD, shares a promising outlook for patients with dry age-related macular degeneration, with innovative therapies in development that have the potential not only to prevent vision loss but also improve visual acuity.

Peter K. Kaiser, MD, sat down with Sheryl Stevenson, Group Editorial Director - Eye Care, to discuss his presentation on emerging therapies for dry age-related macular degeneration at this year’s AAO meeting.

Video Transcript

Editor’s note - This transcript has been edited for clarity.

Sheryl Stevenson: We are joined today by Dr. Peter Kaiser, who is presenting at this year's American Academy of Ophthalmology [AAO] meeting. Welcome to you, Dr. Kaiser. Really excited to learn more about your presentation. Can you tell us more about it regarding non-neovascular drugs in the pipeline?

Peter K. Kaiser, MD: When we look at non-neovascular AMD [age-related macular degeneration], or dry AMD, we have two drugs that are FDA approved. Thankfully, we have many drugs in the pipeline. What we're discussing at AAO would be some of these approaches.

One approach would be to reduce toxic byproduct accumulation. That will be amyloid beta oligomers that form very similar to Alzheimer disease. We have several drugs that are targeting beta amyloid oligomers and preventing that.

Number two, oxidative stress is known to be a big factor in dry macular degeneration so we're looking at several drugs that reduce oxidative stress. And interestingly enough, these drugs actually have been shown in early studies to improve visual acuity. In a Phase 3 study, we're going to try to replicate that with actually improving visual acuity, something we haven't seen with any of our drugs currently.

Visual cycle modulators have been tested for many, many years. And there are still some drugs that target the visual cycle, slowing it down, thereby preventing toxic byproduct accumulation.

Finally, the area that actually has 2 FDA-approved products is the idea of complement modulation. We have drugs that target C3 and C5. Because of the success of both those drugs, there's about 30 other drugs currently in clinical testing in this space, either blocking other portions of the complement cascade, or interestingly enough doing something that the body is against. In other words, we have mutations in complement factor H [CFH] and complement factor I [CFI] that predisposes you to macular degeneration. And so we have gene therapy products that are basically replacing these damaged CFI and CFH proteins with recombinant normal wild type. So we'll see if any of these drugs actually see the light of day, but it's an exciting time in the dry macular degeneration space.

Stevenson: Absolutely. And what are you most excited about for your patients who have these conditions, these these therapies at their disposal possibly in the future?

Kaiser: I'm excited about the drugs that actually are improving vision. All the stuff that we have currently, even the FDA-approved ones, don't really improve visual acuity. They're preventing vision loss. So to actually be able to improve vision in some of our dry macular degeneration patients, improve their visual function, is exciting.

And the other is gene therapy. So right now, our current treatments require injections every month or every other month. And with gene therapy, we may have a lifelong treatment, so only one treatment, and we're done. So those are all the ones that we are super excited about.

Stevenson: Anything else to add that we haven't touched upon?

Kaiser: If you look at the dry macular degeneration space, there's so many drugs in clinical development.

The reason for that is we don't have an animal model. So the only way we could test these drugs are in humans, number one.

Number two, we don't have a smoking gun like wet macular degeneration and we know if we targeted the VEGF protein, we have a pretty good result. Whereas in dry macular degeneration, we don't have that smoking gun. And so there's many approaches being performed. And it's truly an exciting time in drug development for this disease.

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