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. These designations underscore the potential of gildeuretinol to address a significant unmet medical need in this progressive and rare condition that leads to severe vision loss in both children and adults.
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 demonstrated that gildeuretinol can decrease vitamin A dimerization to normal rates, preventing retinal degeneration and loss of visual function in animal models of Stargardt disease.
Clinical Efficacy of Gildeuretinol
Data from the TEASE (Tolerability and Effects of ALK-001 on Stargardt disease) program, most recently presented at the 2024 American Academy of Ophthalmology (AAO) Annual Meeting, highlight the therapeutic potential of gildeuretinol. The TEASE program consists of four independent clinical studies: TEASE-1, TEASE-2, TEASE-3, and TEASE-4.
In the TEASE-1 study, a 24-month, placebo-controlled, double-masked, randomized trial involving patients with Stargardt disease, gildeuretinol demonstrated a statistically significant reduction in the growth rate of atrophic retinal lesions. Specifically, the growth rate of the square root of atrophic retinal lesion area was slowed by 21.6% in the gildeuretinol-treated group compared to the untreated group (p<0.001). A sensitivity analysis using non-transformed values showed a 29.5% reduction in lesion growth. The growth rates were 0.18 mm/year (0.87 mm²/year untransformed area) in the treated arm and 0.23 mm/year (1.23 mm²/year) in the untreated arm, with a mean difference of 0.05 mm/year (95% CI: 0.03 to 0.07, p<0.001).
Interim data from the TEASE-3 study, an open-label trial in early-stage Stargardt disease patients, revealed that treatment with gildeuretinol was associated with disease stabilization. Patients treated early showed no disease progression and remained asymptomatic while on therapy for between two and six years. Furthermore, gildeuretinol treatment in these early-stage patients correlated with relatively stable visual acuity.
FDA Designations and Their Significance
The FDA's Rare Pediatric Disease designation is granted to therapies intended for serious or life-threatening rare diseases primarily affecting individuals from birth to 18 years of age. This designation makes Alkeus eligible for a priority review voucher (PRV) upon approval, which can be used to expedite the development of another clinical program.
The Fast Track designation is reserved for drugs intended to treat serious conditions with clinical data demonstrating the potential to address unmet medical needs. Gildeuretinol has previously received Breakthrough Therapy and Orphan Drug designations from the FDA, further emphasizing its promise as a treatment for Stargardt disease.
Stargardt Disease: An Unmet Medical Need
Stargardt disease is a significant cause of severe vision impairment in children and young adults, affecting an estimated 30,000 to 87,000 individuals in the United States. The disease is characterized by a defect in the ABCA4 protein, leading to accelerated dimerization of vitamin A and the formation of toxic by-products that damage the retina, resulting in progressive vision loss. Currently, there are no approved treatments for Stargardt disease.
Michel Dahan, president and CEO of Alkeus Pharmaceuticals, emphasized the importance of these designations, stating that they highlight the potential for oral gildeuretinol to be a groundbreaking therapy for patients with Stargardt disease. He also acknowledged the significant unmet medical need and the burden on patients and their families.
