The TEASE-3 study by Alkeus Pharmaceuticals Inc. has revealed positive interim results for the treatment of early-stage Stargardt disease using gildeuretinol (ALK-001). Three teenagers participating in the study have remained symptom- and progression-free for up to 6 years, showcasing the potential of gildeuretinol to halt the disease's advancement.
Stargardt disease, an inherited genetic mutation, typically begins causing visual symptoms in childhood or adulthood and progresses to vision loss and blindness due to the accumulation of material in the retina. Michael B. Gorin, MD, PhD, expressed optimism about the results, highlighting the dramatic preservation of vision in younger patients.
Gildeuretinol is a novel molecule, a specialized form of deuterated vitamin A, designed to reduce the dimerisation of vitamin A without disturbing vision. The drug targets the mutation in the ABCA4 gene, which leads to the accumulation of byproducts and retinal damage in Stargardt disease.
In the TEASE-1 trial, gildeuretinol slowed disease progression in patients with more advanced Stargardt disease but did not stop it, unlike the results seen in the TEASE-3 study with early-stage disease. The TEASE-3 study, an open-label trial, enrolled patients with early signs of disease visible on retinal imaging but without symptoms of vision loss. The study's primary end-point measures progression after the first 2 years of treatment, with patients able to continue receiving gildeuretinol for extended periods.
The TEASE-2 trial, an ongoing, fully enrolled, randomised, triple-masked, placebo-controlled trial, involves 80 patients with Stargardt disease, with top-line data expected in 2025. Gildeuretinol has received breakthrough therapy and orphan drug designations by the US FDA.
The theory behind vision loss in Stargardt disease involves the ABCA4 gene mutation, leading to vitamin A accumulation in cells, forming toxic products that trigger cell death and vision loss. Current therapies aim to reduce vitamin A uptake, provide modified vitamin A, remove lipofuscin from cells, and block complement activation in eye cells.
The TEASE-3 study's unique design allowed asymptomatic patients from highly motivated families to undergo molecular genetic testing with the expectation of receiving gildeuretinol if they had the same mutations as their affected siblings. This approach addressed ethical considerations and provided comparative, age-matched data from siblings, offering a reasonable strategy to study this rare disease.
Gildeuretinol's success in the TEASE-3 study represents a significant step forward in treating Stargardt disease, offering hope for preserving vision in patients with early-stage disease.
