Gildeuretinol in Early-Stage Stargardt Disease: TEASE-3

Dr. Kondapalli: Stargardt’s disease is an inherited retinal disease that’s usually transmitted in autosomal-recessive fashion, traditionally believed associated with a mutation of the ABCA4 gene. This mutation leads to retinal damage because the protein that the ABCA4 gene codes for essentially causes accumulation of by-products. So, vitamin A is one of those by-products, and it accumulates in the cells, triggering the complement system. Those of us who specialize in retinal disease are very familiar with the complement system in terms of what happens in dry macular degeneration or geographic atrophy. But what’s interesting in Stargardt’s disease is that it too triggers the complement system, resulting in cell death and ultimately vision loss. And so, it’s unfortunate, and sometimes patients can be diagnosed at a really young age, and, ultimately, the result is significant vision loss.

Effect of gildeuretinol in Stargardt disease

Of note, gildeuretinol is the novel molecule that Alkeus Pharmaceuticals is looking at, a specialized form of deuterated vitamin A. This molecule is supposed to reduce the demineralization of vitamin A without disturbing vision. And we know that vitamin A accumulation can lead to cell death and ultimately cause the complement system to overrun in Stargardt’s disease, resulting in vision loss.

Aims of the TEASE-3 trial

TEASE-3 is an open-label study that is looking at younger patients who have been diagnosed with Stargardt’s disease but have yet to have any visual compromise The trial is investigating if gildeuretinol — the ALK-001 molecule — can actually halt or prevent visual damage in those patients.

The trial enrolled a total of 3 teenagers. And what is interesting is that they’ve remained symptom-free throughout their treatment cycle. Of the 3 patients, 1 has remained symptom-free for 2 years, and 2 patients are out to 6 years, and none of them has shown any sort of disease progression.

Other TEASE trials

The other thing to note is that this is not the first time this molecule’s been investigated. TEASE-3 is an open-label study looking at specifically younger patients without symptomatic Stargardt’s disease. However, TEASE-1, which was the initial trial, showed a 21% reduction in the growth rate of atrophic lesions in 50 patients with Stargardt’s disease. TEASE-2 is completely enrolled, and that is looking at 80 patients with Stargardt’s disease, with top-line data expected to be released later this year. And TEASE-4 is an open-label extension study, which will be continuing, hopefully with a read out later in 2025 or 2026.