AAO 2024: Deuterated vitamin A preserves vision in Stargardt disease

Christine N. Kay, MD, discussed her presentation, "Deuterated vitamin A preserves vision in Stargardt’s disease (TEASE study)" which was given at this year's American Academy of Ophthalmology meeting held in Chicago, Illinois.

Video Transcript:

Editor's note: The below transcript has been lightly edited for clarity.

Sydney M. Crago: Hi. I'm Sydney Crago from Modern Retina and Ophthalmology Times, and I'm here today with Dr Christine Kay to talk a little bit about the TEASE study and her presentation at AAO. Dr Kay, can you share a little bit about this presentation?

Christine N. Kay, MD: Sure, and by way of introduction, again, my name is Christine Kay. I'm a vitreoretinal surgeon, and I'm an inherited retinal disease specialist at Vitreo Retinal Associates, which is a practice in Gainesville, Florida. And I had the opportunity to present at AAO 2024 in Chicago, some data from the Alkeus sponsored trial. The talk was entitled Gildeuretinol slows progression of Stargardt disease: The TEASE program. So just for a bit of background, Stargardt disease is the most common form of inherited macular degeneration with a juvenile onset, typically. With a prevalence of approximately 1 out of 8000–so fairly common retinal dystrophy. Patients with Stargardt disease, develop a central blind spot, eventually leading to legal blindness status, typically in the 20/200 range of visual acuity. And this happens over time. These patients first start with a central blind spot in their macula, which is the central spot of their retina, and they develop this atrophic lesion atrophy, meaning areas that have degenerated. And this expands over time. Ninety-five percent of patients with Stargardt disease carry 2 mutations. So it's a genetic disease, genetically inherited disease, and they carry these 2 mutations in the ABCA4 gene.

The TEASE program was a set of clinical trials developed by a company, Alkeus pharmaceutical. They developed a drug called gildeuretinol. And gildeuretinol is a molecularly modified form of vitamin-A, which is a necessary part of the visual cycle. So we can't just eliminate vitamin-A. But vitamin-A is also in Stargardt disease patients problematic because of this ABCA4 defect, they can't process the byproducts of the natural visual cycle. So what gildeuretinol does is slow down the byproduct formation, something called dimerization in the vitamin-A pathway, but importantly, still allowing the visual cycle to occur normally, so that patients don't have dark adaptation or night-blindness problems, which occur if you stop the visual cycle. So the gildeuretinol drug allows that visual cycle to occur, but doesn't allow the same buildup of the byproducts of vitamin-A which cause the atrophic lesion and retinal degeneration over time in Stargardt patients.

And what this trial does, and what I presented at AAO 2024, and the TEASE 1 study data, the gildeuretinol drug, which is orally taken by mouth, slowed the progression of the atrophic lesion in Stargardt disease patients to a statistically significant level of 21% reduction in patients with Stargardt disease compared to placebo patients. So again, that 21% reduction in patients with treatment versus patients without treatment. So this was exciting data. Importantly, the safety profile was also excellent. There were not reports of dark adaptation or night-blindness or any significant lab issues with these patients. So very safe, orally taken therapy that does show efficacy. So exciting data. It's exciting to be able to stand at Academy of Ophthalmology and give this update.

I did also overview and give a landscape picture of the other TEASE studies. There's a TEASE 2, 3 and 4 study that I gave a little bit of an overview of, and the TEASE 2 program will have its top line release in early 2025 we expect. So in conclusion, Stargardt disease is a common form of inherited retinal degeneration causing an atrophic lesion. It's genetically caused with patients with ABCA4 mutations the gildeuretinol drug slowed progression of the atrophic lesion in Stargardt patients with a 21% reduction in that growth of that atrophic lesion in patients who were treated versus untreated patients. The safety profile was excellent. This is actually the first randomized controlled trial in Stargardt disease to show an efficacy event in patients with Stargardt disease. So that's exciting data. The gildeuretinol drug and the Alkeus program have orphan drug status, as well as the breakthrough designation status from the FDA, again, exciting times for patients with Stargardt disease, as well as for doctors taking care of these patients. So thank you very much.