Alkeus’ Gildeuretinol Studied to Halt Progression of Early-Stage Stargardt Disease

Alkeus Pharmaceuticals announced positive interim data showing gildeuretinol halted Stargardt disease progression for up to 6 years in the ongoing TEASE-3 clinical trial.

The first three teenage patients with early-stage Stargardt disease enrolled in the trial and treated with oral gildeuretinol acetate (ALK-001) remained asymptomatic and free of disease progression for their treatment duration ranging between 2 years (one patient) and 6 years (two patients).

The company noted that in the absence of treatment, the patients were projected to begin experiencing vision loss within 2 years, following the same disease trajectory as that of their respective older siblings with identical genetic mutations who had not been treated with gildeuretinol.

Gildeuretinol acetate is a novel molecule created as a specialized form of deuterated vitamin A designed to reduce the dimerization of vitamin A without disrupting vision. Gildeuretinol has received the FDA’s breakthrough therapy designation and orphan drug designation. In preclinical studies, gildeuretinol decreased vitamin A dimerization to the normal rate seen in unaffected individuals and prevented retinal degeneration and blindness in animals with Stargardt disease.

“I am encouraged by the results of the different TEASE trials,” commented Michael B. Gorin, MD, in Alkeus’ press release. “Both the initial TEASE-1 study and this smaller cohort of early-stage Stargardt patients show clinical benefits from gildeuretinol. However, the dramatic preservation of vision in these younger patients highlights the need to consider the impact of therapies at different stages of the condition.”

Dr. Gorin, who is from the Departments of Ophthalmology and Human Genetics at the David Geffen School of Medicine at UCLA in Los Angeles, California, continued, “Usually, such asymptomatic or minimally symptomatic individuals are excluded from clinical trials. Being able to compare even this small number of individuals with the severity of disease in their older, untreated siblings who share the same genetic etiology, as well as the same dietary and environmental exposures, allows us to draw meaningful insights into the potential of this medication to preserve sight.”

According to Alkeus, the TEASE-3 clinical trial is an open-label study of gildeuretino in early-stage Stargardt disease. Patients is the study have early signs of disease visible on retinal imaging but have not begun experiencing symptoms of vision loss.

Fundus autofluorescence imaging and other outcome measures were used to assess the extent to which gildeuretinol affects disease progression. Year-over-year progression was assessed, as well as age-matched comparison to each participant’s untreated sibling with Stargardt disease and identical mutations. The primary endpoint is a measure of progression after the first two years of treatment. After the initial 2-year treatment, patients can continue to receive gildeuretinol for extended periods.

Alkeus noted that the TEASE trials consist of four independent clinical studies of gildeuretinol in Stargardt disease:

• TEASE-1 study was a randomized, triple-masked, placebo-controlled trial in 50 randomized patients with Stargardt disease. Gildeuretinol met its prespecified primary efficacy endpoint showing a 21% reduction in the growth rate of retinal atrophic lesions (P < .001, square root units, 28% effect for untransformed areas) against untreated patients. Gildeuretinol was well-tolerated.
• TEASE-2 trial is an ongoing, fully enrolled, randomized, triple-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. The trial has enrolled a total of five patients to date with no signs of disease progression while on treatment.
• TEASE-4 is an open-label extension study.

In addition to the TEASE trials, a phase 3 study of gildeuretinol in 200 patients with geographic atrophy secondary to age-related macular degeneration has recently been completed and is expected to have topline data in 2024.

“The data show the potential of gildeuretinol acetate to arrest Stargardt disease when treatment is started early,” stated Leonide Saad, PhD, President and CEO of Alkeus Pharmaceuticals, in the press release. “These early results of TEASE-3, together with the results of TEASE-1 in more advanced disease, recently presented at the American Academy of Ophthalmology, show great promise for all patients. We look forward to submitting a new drug application for gildeuretinol acetate in the treatment of Stargardt disease.”