Christine Kay, MD, of Vitreo Retinal Associates in Gainesville, Florida, discusses results of the TEASE study, presented at the 2024 AAO Annual Meeting.
Christine Kay, MD:
I had the honor this year at the American Academy of Ophthalmology 2024 in Chicago presenting an Alkeus presentation on [how] gildeuretinol slows progression of Stargardt disease, the TEASE program. In this talk, I gave the background of Stargardt disease. Stargardt disease is the most common form of inherited macular degeneration with a juvenile onset. It’s actually a relatively common inherited retinal dystrophy, with a prevalence of one out of 8,000 patients with Stargardt disease developing a central blind spot in the retina, similar to macular degeneration patients. This happens at a much younger age for Stargardt disease patients. They can progress to 20/200 visual acuity, which is the social security definition of legal blindness or slightly worse visual acuity over time. This happens because of the growth of an atrophic lesion, which is retinal degeneration in the central retina known as the macula in these patients.
This happens because of a defect in an ABCA4 gene; 95% of patients with Stargardt disease have the genetic form of this, which is related to 2 mutations in an ABCA4 gene. What the gildeuretinol drug that has been developed by Alkeus does is it is an orally delivered form of molecularly modified vitamin A. That means that the vitamin A is still processing through the eye, but it has been molecularly modified with a deuterated form. That means that one of the hydrogens has been replaced with the deuterium ion. Importantly, what it ends up doing is it allows the visual cycle to occur normally so patients don’t have abnormal dark adaptation or other visual cycle issues or night blindness, which is what would happen if you just deprived yourself of vitamin A. But this molecularly modified form of vitamin A does not dimerize, which means doesn’t build up the same amount of byproduct.
In Stargardt disease patients, these byproducts become toxic and cause that atrophic lesion. In fact, the top-line data of the TEASE 1 study, which I overviewed at this AAO 2024, had met its primary endpoint. This was a randomized, controlled, double-masked study where patients were either treated with gildeuretinol, which is this molecularly modified form of vitamin A, or they were on placebo. There was a 21% reduction in the growth of the atrophic lesion at the end point in this study. That was statistically significant. Importantly, the safety profile was also excellent. The drug was well tolerated. Again, it was administered once a day orally. Patients were followed, blood work, etc. This was all an excellent tolerated safety profile. In summary, I had the of being able to present at Academy this year, the top-line data from the TEASE studies.
I did also overview the other TEASE programs, TEASE 2, TEASE 3, and TEASE 4. At this point, giving an overview of design of these studies, the TEASE 2 top-line data is expected to be released in 2025. Regarding the Alkeus program, this is the first randomized, controlled trial in Stargardt disease, which currently has no FDA-proof treatment that has shown an efficacy end point. The FDA has actually given the Alkeus gildeuretinol drug an orphan drug status, as well as breakthrough designation status, which is very exciting as an inherited retinal disease specialist taking care of patients with Stargardt disease and I’m sure to my Stargardt disease patients. Thank you very much and it was wonderful being able to present this data at Academy this year.
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