Michael B. Gorin, MD, PhD: Interim TEASE-3 Trial Data in Stargardt Disease

Positive interim data from the TEASE-3 clinical trial show gildeuretinol (ALK-001) slows the progression of Stargardt disease, the most common form of inherited macular degeneration in children and young adults, for up to six years.

Announced by Alkeus Pharmaceuticals, results from TEASE-3 showed the first 3 patients treated with oral gildeuretinol have remained asymptomatic and free from disease progression over their treatment duration, ranging between 2 years and 6 years. Without gildeuretinol treatment, patients were projected to experience vision loss within 2 years.

“We could find evidence of early Stargardt changes with microperimetry or imaging, but they were completely asymptomatic. From a vision standpoint, they were functioning completely normally,” Michael B. Gorin, MD, PhD, departments of ophthalmology and human genetics, David Geffen School of Medicine, UCLA, told HCPLive. “Those children who have been on this drug have managed to maintain a high level of vision and have developed almost no atrophy at all.”

An estimated 30,000 people in the United States and more than 150,000 globally are projected to be affected by Stargardt disease. These individuals exhibit a defective ABCA4 protein, which results in the accelerated dimerization of Vitamin A, leading to toxic by-products that irreversibly damage the retina and lead to progressive vision loss.

The open-label TEASE-3 trial is the first clinical trial in early-stage Stargardt disease, investigating the use of gildeuretinol. These participants have early signs of disease but do not yet experience symptoms of vision loss. The trial analyzed year-over-year progression in each participant and an age-matched comparison to each participant’s sibling with Stargardt disease and identical mutations, who was not treated with gildeuretinol.

TEASE-3’s primary endpoint consisted of progression after the first 2 years of treatment. After the initial two-year treatment, patients can continue to undergo gildeuretinol treatment for extended periods. Of the 5 participants enrolled in TEASE-3, the study reports no signs of disease progression with gildeuretinol treatment.

Topline data from the TEASE-1 trial were presented last year at the 127th Annual American Academy of Ophthalmology Meeting. In TEASE-1, gildeuretinol met its prespecified primary efficacy endpoint, exhibiting a 21% reduction in the growth rate of retinal atrophic lesions (P <0.001 28% effect for untransformed areas) versus the placebo-treated control arm.

“We have an unmet need with no current FDA-approved therapy yet for Stargardt Disease. These patients rapidly go blind to a visually legally blind status over 10 years, usually in late childhood, or early adolescence,” presenting investigator Christine N. Kay, MD, told HCPLive. “It is a visually disabling disease that we would like to be able to treat and halt progression, if possible.”

For more insight into the interim results from the TEASE-3 trial, watch the full interview with Gorin.

Gorin reports no financial disclosures with Alkeus Pharmaceuticals.