Alkeus Pharmaceuticals' investigational oral therapy, gildeuretinol (ALK-001), has been granted Rare Pediatric Disease and Fast Track Designations by the FDA for the treatment of Stargardt disease. This announcement underscores the potential of gildeuretinol to address a critical unmet need in pediatric and young adult patients suffering from this inherited retinal disease.
Gildeuretinol is a novel chemical entity designed to reduce the dimerization of vitamin A without disrupting the visual cycle. Stargardt disease, affecting an estimated 30,000 to 87,000 individuals in the United States, leads to severe vision impairment, and currently, there are no approved treatments available.
The efficacy and safety of gildeuretinol are being evaluated in the TEASE (Tolerability and Effects of ALK-001 on Stargardt diseasE) clinical program, which includes four independent studies: TEASE-1, TEASE-2, TEASE-3, and TEASE-4.
TEASE-1 Trial Results
TEASE-1, a randomized, double-masked, placebo-controlled trial involving 50 Stargardt disease patients, met its primary endpoint. The results demonstrated a statistically significant 21.6% reduction in the growth rate of retinal atrophic lesions area (square root) in the gildeuretinol-treated arm compared to the placebo arm (P < 0.001). Furthermore, a 29.5% reduction was observed for untransformed areas of retinal atrophic lesions.
Specifically, the growth rates of atrophic retinal lesions were 0.18 mm/year (0.87 mm²/year untransformed area) in the gildeuretinol group and 0.23 mm/year (1.23 mm²/year) in the untreated group (mean difference 0.05 mm/year; 95% confidence interval, 0.03 to 0.07, [ P <0.001]). Non-transformed analysis showed a difference of 0.36 mm²/year with a 95% confidence interval of 0.23 to 0.50 (P < 0.001).
Ongoing and Future Studies
TEASE-2, an ongoing randomized, double-masked, placebo-controlled trial, has fully enrolled 80 patients with a moderate stage of Stargardt disease. Data from this study is anticipated in 2025.
TEASE-3 is an open-label study focusing on patients with early-stage Stargardt disease. This trial aims to assess the potential of gildeuretinol in genetically confirmed patients exhibiting early signs of the disease visible on retinal imaging but who have not yet experienced symptoms of vision loss.
Expert Commentary
Dr. Christine Nichols Kay from Vitreo Retinal Associates, Gainesville, Florida, who presented data from the TEASE program at the 2024 American Academy of Ophthalmology annual meeting in October, stated, "TEASE-1 is the first randomized, controlled trial in Stargardt disease that has shown an efficacy endpoint, which is very exciting as an inherited retinal disease specialist taking care of patients with this devastating condition."
Dr. Kay further added, "In addition, the TEASE-3 data indicate the potential value of treating patients with Stargardt disease as early as possible, before onset of progressive central vision loss."
Company Perspective
Michel Dahan, president and CEO of Alkeus Pharmaceuticals, commented, "Receiving both the FDA’s Rare Pediatric Disease and Fast Track designations are important milestones for Alkeus that highlight the potential for oral gildeuretinol to be a groundbreaking therapy for patients."
Dahan also noted that these designations, along with previously awarded Breakthrough Therapy and Orphan Drug designations, "recognize the significant unmet medical need in Stargardt disease and the overwhelming burden on patients as well as their families and caregivers."
