Alkeus Pharmaceuticals has announced positive interim data from its TEASE-3 study, demonstrating that oral gildeuretinol acetate prevented disease progression in early-stage Stargardt disease patients. The study, an open-label trial, showed that patients treated with the drug maintained stable visual acuity over multiple years. These findings, presented at the J.P. Morgan Healthcare Conference, suggest that gildeuretinol could potentially transform the treatment of this rare and progressive condition that leads to irreversible blindness.
Michel Dahan, President and CEO of Alkeus Pharmaceuticals, stated, "These dramatic results showing preservation of vision in early-stage patients highlight the potential of gildeuretinol to prevent children diagnosed with Stargardt disease from progressing to severe vision loss when therapy is started early." The company plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for gildeuretinol as a treatment for Stargardt disease as early as possible in 2025.
TEASE-3 Study Details
The TEASE-3 study enrolled patients with early signs of Stargardt disease visible on retinal imaging but who had not yet experienced symptoms of vision loss. The primary endpoint was a measure of disease progression after the first two years of treatment, assessed using fundus autofluorescence (FAF) imaging and other outcome measures. Following the initial two-year treatment, patients could continue to receive gildeuretinol as part of an extension study. To date, TEASE-3 has enrolled a total of seven patients.
Seemi Khan, MD, MBA, Chief Medical Officer at Alkeus Pharmaceuticals, noted, "Two additional patients have completed 24 months of treatment in the TEASE-3 study, and the results demonstrated that once-daily oral gildeuretinol prevented progression and vision remained stable with a consistent, well-tolerated safety profile." Furthermore, the initial three participants who completed the study and remained on treatment for multiple years have continued to show no progression, with the longest duration of therapy to date being more than seven years.
Stargardt Disease and Gildeuretinol Mechanism
Stargardt disease affects an estimated 30,000 people in the U.S. and is characterized by a defect in the ABCA4 protein, leading to the accumulation of toxic vitamin A dimers that damage the retina. Currently, there is no FDA-approved treatment for the condition.
Gildeuretinol acetate (ALK-001) is a new chemical entity designed to reduce the dimerization of vitamin A without modulating the visual cycle. Preclinical studies have shown that gildeuretinol decreases vitamin A dimerization down to the normal rate and prevents retinal degeneration and loss of visual function in animal models of Stargardt disease. In a randomized, placebo-controlled, double-masked clinical trial of gildeuretinol in late-stage Stargardt patients (TEASE-1), the drug demonstrated a clinically and statistically significant slowing of the growth of retinal lesions over two years of treatment (p<0.001).
Broader TEASE Program
The TEASE program encompasses four independent clinical studies of oral gildeuretinol (ALK-001) in Stargardt disease: TEASE-1, TEASE-2, TEASE-3, and TEASE-4. The TEASE-1 study, a randomized, double-masked, placebo-controlled trial in 50 patients, met its prespecified primary efficacy endpoint, showing a 21.6% reduction in the growth rate of retinal atrophic lesions area (square root) and a 29.5% reduction for untransformed areas of retinal atrophic lesions against untreated patients. Gildeuretinol was well-tolerated in this study. The TEASE-2 trial is an ongoing, fully enrolled, randomized, double-masked, placebo-controlled trial in 80 patients with moderate Stargardt disease, with topline data expected in 2025. TEASE-4 is an open-label extension study.
With Breakthrough Therapy, Rare Pediatric Disease, Fast Track, and Orphan Drug designations for Stargardt disease from the FDA, gildeuretinol represents a promising therapeutic option for this debilitating condition.
