The FDA has granted Rare Pediatric Disease and Fast Track designations to gildeuretinol acetate (ALK-001), an investigational oral therapy developed by Alkeus Pharmaceuticals, for the treatment of Stargardt disease. This rare and serious pediatric condition currently lacks approved treatments. The designations are supported by positive data from Alkeus' TEASE program.
Promising Results from TEASE Trials
Data presented at the 2024 American Academy of Ophthalmology annual meeting highlighted the efficacy of gildeuretinol. The TEASE-1 trial, a 24-month, placebo-controlled, double-masked, randomized study, demonstrated that gildeuretinol slowed the growth rate of atrophic retinal lesions by 21.6% compared to untreated patients. Specifically, the growth rates of atrophic retinal lesions were 0.18 mm/year in the gildeuretinol treated arm and 0.23 mm/year in the untreated arm. A sensitivity analysis using non-transformed values showed a 29.5% reduction in growth rate of atrophic lesions with gildeuretinol (0.87 mm²/year vs 1.23 mm²/year, difference of 0.36 mm²/year, 95% CI, 0.23-0.50; p < .001).
Interim data from the TEASE-3 study further indicated that early-stage Stargardt disease patients treated with gildeuretinol showed no disease progression and remained asymptomatic while on therapy for between 2 and 6 years. Treatment was also associated with relatively stable visual acuity. Both TEASE-1 and TEASE-3 demonstrated a favorable safety and tolerability profile.
Expert Commentary
"TEASE-1 is the first randomized, controlled trial in Stargardt disease that has shown an efficacy end point," said Dr. Christine Nichols Kay, an inherited retinal disease specialist. "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."
Stargardt Disease and Gildeuretinol Mechanism
Stargardt disease leads to vision impairment in children and young adults, affecting an estimated 30,000 to 87,000 people in the US. The disease is characterized by a central blind spot due to a defective ABCA4 protein, which results in accelerated dimerization of vitamin A and irreversible damage to the retina. Gildeuretinol is designed to reduce vitamin A dimerization without disrupting the visual cycle. Preclinical studies have suggested that gildeuretinol can decrease vitamin A dimerization to a normal rate, preventing retinal degeneration and vision loss in animal models of Stargardt disease.
Ongoing Clinical Trials
Alkeus Pharmaceuticals is continuing to evaluate gildeuretinol in additional clinical trials, including TEASE-2 and TEASE-4, as part of the broader TEASE program.
