ASRS 2024: TEASE-3 study data shows progression stalled in early-stage Stargardt disease patients treated with gildeuretinol

(Image credit: Sydney M. Crago)

Alkeus Pharmaceuticals Inc announced the presentation of interim data from its TEASE-3 study that showed early-stage Stargardt disease patients treated with gildeuretinol acetate exhibited no disease progression and remained asymptomatic while on therapy ranging between 2 and 6 years.

Details of the study were presented during the 42nd American Society of Retina Specialists (ASRS) Annual Scientific Meeting, being held July 17-20 in Stockholm, Sweden.

According to a news release, gildeuretinol acetate (ALK-001) is a novel molecule created as a specialized form of deuterated vitamin A designed to reduce the dimerization of vitamin A without disrupting vision. In preclinical studies, gildeuretinol decreased vitamin A dimerization to the normal rate seen in unaffected individuals and prevented retinal degeneration and loss of visual function in animals with Stargardt disease.¹

The company noted that gildeuretinol has received orphan drug designation and breakthrough therapy designation from the FDA. In addition to the TEASE trials, a Phase 3 (SAGA) study of gildeuretinol in 200 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is expected to read out topline data in 2024.

Seemi Kahn, MD, MPH, MBA, chief medical officer of Alkeus Pharmaceuticals, pointed out in a news release that interim results from the TEASE-3 study of gildeuretinol in early-stage Stargardt patients indicate the potential value of treating patients with confirmed disease-causing ABCA4 genetic mutations as early as possible before the disease causes progressive loss of central vision.¹

“There is high unmet need in this disease area with no existing treatment, and we look forward to sharing additional results from this encouraging study in the future as we work to advance our development program, which has the potential to be the first therapy for Stargardt disease,” Kahn said in the release.

TEASE-3, the first clinical trial in early-stage Stargardt disease, is an open-label study of gildeuretinol in genetically confirmed patients with early signs of disease visible on retinal imaging, but who have not begun experiencing symptoms of vision loss. Each TEASE-3 study participant has a sibling who was previously diagnosed with Stargardt disease, has identical gene mutations and has experienced irreversible vision loss.¹

The primary endpoint of disease progression over 2 years is assessed by retinal imaging and functional outcome measures. After the initial 2-year treatment period, patients continue to receive gildeuretinol while enrolled in an open label long-term extension study. The TEASE-3 study has enrolled a total of 6 patients, who receive gildeuretinol as a once-a-day pill.¹

Michael B. Gorin, MD, PhD, of the Departments of Ophthalmology and of Human Genetics at the David Geffen School of Medicine at UCLA, pointed out in the news release the TEASE-3 study has proved to be a unique opportunity to evaluate gildeuretinol in a small group of presymptomatic children for whom we had clinical history information regarding the course of Stargardt disease in older siblings.

“We were able to assess the ability of the medication to stall vision loss in these children as compared to the age-matched data of their genetically-matched Stargardt siblings,” he said in the news release. “The dramatic delay of vision and photoreceptor loss in this small cohort is an exciting advancement in the therapy for ABCA4-related Stargardt disease and suggests that the clinical benefits may be greater at the earliest stages of this condition.”

Stargardt disease is a serious cause of blindness in children and young adults, with an estimated 30,000 people affected in the United States and more than 150,000 worldwide. There is no approved treatment.

In individuals diagnosed with Stargardt disease, the ABCA4 protein is defective, which leads to the accelerated dimerization of vitamin A, forming toxic by-products that result in irreversible damage the retina, resulting in progressive vision loss.

TEASE Trials

The TEASE trials consist of four clinical studies of gildeuretinol acetate (ALK-001) in Stargardt disease, denoted as TEASE-1, TEASE-2, TEASE-3 and TEASE-4. The TEASE-1 study was a randomly assigned, double-masked, placebo-controlled trial in 50 patients with Stargardt disease. Gildeuretinol met its prespecified primary efficacy endpoint showing a 21% reduction in the growth rate of retinal atrophic lesions (p <0.001, square root units, 28% reduction for untransformed areas of retinal atrophic lesions) against untreated patients. Gildeuretinol was well-tolerated.

The TEASE-2 trial is an ongoing, fully enrolled, randomly assigned, double-masked, placebo-controlled trial in 80 patients with Stargardt disease, expected to read out topline data in 2025. TEASE-3 is an open-label study designed to assess gildeuretinol in early-stage Stargardt patients. TEASE-4 is an open-label extension study.

Reference:

1. Pharmaceuticals A. Alkeus Pharmaceuticals Announces Presentation of a TEASE-3 Study Update Showing Progression Stalled in Early-Stage Stargardt Disease Patients Treated with Gildeuretinol. GlobeNewswire News Room. Published July 18, 2024. Accessed July 18, 2024. https://www.globenewswire.com/news-release/2024/07/18/2915423/0/en/Alkeus-Pharmaceuticals-Announces-Presentation-of-a-TEASE-3-Study-Update-Showing-Progression-Stalled-in-Early-Stage-Stargardt-Disease-Patients-Treated-with-Gildeuretinol.html