Interim data from the ongoing TEASE-3 study, presented at the 2025 American Society of Retina Specialists (ASRS) meeting in Long Beach, California, suggest that an investigational oral therapy may help preserve vision and slow anatomic progression in children and adolescents with early-stage Stargardt disease.
Stargardt disease is caused by mutations in the ABCA4 gene, which impair the clearance of retinal byproducts in photoreceptor cells. This leads to the accumulation of toxic bisretinoids, particularly A2E, in the retinal pigment epithelium, where they contribute to cell dysfunction and atrophy over time. Gildeuretinol (ALK‑001; Alkeus Pharmaceuticals) is a new molecular entity designed to reduce the dimerization of vitamin A and reduce these toxic biproducts without modulating the visual cycle. By limiting A2E accumulation, gildeuretinol aims to slow the progression of retinal degeneration in Stargardt disease. The drug has received orphan drug, rare pediatric disease, breakthrough therapy, and fast track designations from the US Food and Drug Administration (FDA).
TEASE-3 includes children as young as 8 years old with early structural signs of Stargardt but minimal symptoms. Each participant treated with gildeuretinol has a sibling who also has Stargardt; the trial evaluates the effect of gildeuretinol on disease progression compared to patients’ baseline measures as well as siblings’ images and data. Kenneth C. Fan, MD, MBA, of Retina Consultants of Texas, shared data from 6 patients, 5 of whom completed 24 months of gildeuretinol treatment. The findings showed stable visual acuity and slower anatomic degeneration, compared with historical data from affected siblings who had not received treatment with the compound.
“The visual acuity for the patients on gildeuretinol remains relatively stable throughout the entire follow-up period,” said Dr. Fan, whose research focuses on inherited retinal diseases. “And for siblings with age-matched historical data, you can see that there’s gradual loss of visual acuity over the same period. Watching that change in vision and the disparity between the siblings is quite stark in some cases.”
The comparison extended beyond acuity. Imaging data showed a slower rate of ellipsoid zone (EZ) area loss, an established biomarker of atrophy in Stargardt disease, in patients receiving gildeuretinol. “There is a reduction or a minimal increase in EZ area loss over several years on gildeuretinol-treated patients as compared to their historical siblings,” Dr. Fan said.
Similarly, fundus autofluorescence remained stable in treated participants, while increased atrophy was observed in siblings over a comparable period. These differences, he noted, were particularly visible in 2 of the sibling pairs.
No drug-related serious adverse events were reported in TEASE-3, and no participant discontinued the study because of side effects. Dr. Fan said systemic monitoring—including liver function tests and lipid panels—showed either no change or only minor variation over the course of treatment.
“We know that the natural history of early onset Stargardt disease tends to be more aggressive with more rapid vision loss,” Dr. Fan said. “So that’s a huge window of opportunity for treatment.”
TEASE-3 is 1 of 4 clinical trials in Alkeus’s TEASE program. TEASE-1 was a placebo-controlled randomized study in patients with established atrophy. TEASE-2 includes participants with early functional loss but no atrophy. Enrollment in TEASE-3 remains ongoing, with a target of 20 patients. Because of the rarity of Stargardt disease and the challenge of identifying sibling pairs, recruitment is difficult, explained Dr. Fan. All TEASE-3 patients who completed 24 months of treatment will continue into TEASE-4, a long-term extension study for the earlier cohorts.
Gildeuretinol is also being studied for geographic atrophy; data from the phase 2 SAGA trial was reported at the 2024 American Academy of Ophthalmology (AAO) meeting. RP