Alkeus Pharmaceuticals, Inc. has announced that its investigational oral therapy, gildeuretinol (ALK-001), has been granted Rare Pediatric Disease and Fast Track designations by the U.S. Food and Drug Administration (FDA) for the treatment of Stargardt disease. These designations underscore the significant unmet need for effective treatments for this rare and serious pediatric condition, for which no approved therapies currently exist.
Michel Dahan, President and CEO of Alkeus Pharmaceuticals, stated, "Stargardt disease is a serious and relentlessly progressive rare condition leading to severe vision loss in children and adults, and there is no approved treatment available." He further emphasized that these designations highlight the potential of gildeuretinol as a groundbreaking therapy for patients, building upon previous Breakthrough Therapy and Orphan Drug designations.
Clinical Data from the TEASE Program
Data from Alkeus’ TEASE (Tolerability and Effects of ALK-001 on Stargardt diseasE) program were presented at the 2024 American Academy of Ophthalmology annual meeting. The TEASE program consists of four independent clinical studies evaluating oral gildeuretinol in Stargardt disease.
In the TEASE-1 study, a 24-month, placebo-controlled, double-masked, randomized trial, gildeuretinol demonstrated a statistically significant slowing of the growth rate of atrophic retinal lesions by 21.6% compared to untreated patients (p<0.001). 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, with a mean difference of 0.05 mm/year (95% CI: 0.03 to 0.07). A sensitivity analysis using non-transformed values showed a 29.5% reduction in growth rate.
Interim data from the TEASE-3 study indicated that early-stage Stargardt disease patients treated with gildeuretinol showed no disease progression and maintained stable visual acuity while on therapy for two to six years. These patients remained asymptomatic throughout the treatment period.
Safety and Tolerability
In both TEASE-1 and TEASE-3, gildeuretinol exhibited a favorable safety and tolerability profile. Notably, there were no adverse events related to hyper- or hypo-vitaminosis A, such as xerophthalmia, chromatopsia, dark adaptation delays, or night blindness.
About Stargardt Disease
Stargardt disease is a leading cause of severe vision impairment in children and young adults, affecting an estimated 30,000 to 87,000 individuals in the U.S. The disease is characterized by a defect in the ABCA4 protein, leading to the accelerated dimerization of vitamin A and the formation of toxic by-products that damage the retina, resulting in progressive vision loss.
Regulatory Pathway and Future Plans
The FDA's Rare Pediatric Disease designation allows Alkeus to potentially receive a priority review voucher (PRV) upon approval of gildeuretinol, which can be used to expedite the review of another clinical development program. Alkeus plans to apply for a PRV along with its New Drug Application (NDA) submission for gildeuretinol. The Fast Track designation facilitates the development and accelerates the review of drugs intended to treat serious conditions with unmet medical needs.
Christine Nichols Kay, M.D., of Vitreo Retinal Associates, commented on the TEASE-1 results, stating, "TEASE-1 is the first randomized, controlled trial in Stargardt disease that has shown an efficacy endpoint, which is very exciting." She also highlighted the potential value of early intervention, noting that the TEASE-3 data suggest the benefits of treating patients as early as possible, before the onset of progressive central vision loss.
