Alkeus Pharmaceuticals announced that gildeuretinol (ALK-001), an investigational oral therapy, has received Rare Pediatric Disease and Fast Track designations from the FDA for the treatment of Stargardt disease. These designations underscore the significant unmet need in Stargardt disease, a rare and serious pediatric condition for which no approved treatment exists.
FDA Designations and Their Significance
The FDA grants Rare Pediatric Disease designation to therapies intended to treat serious or life-threatening rare diseases primarily affecting individuals from birth to 18 years of age. This designation allows Alkeus to potentially receive a priority review voucher (PRV) upon approval, which can be used to expedite the review of another clinical development program. The Fast Track designation is granted to drugs intended to treat a serious condition with clinical data demonstrating the potential to address an unmet medical need. Gildeuretinol has previously received Breakthrough Therapy and Orphan Drug designations from the FDA.
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. 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."
TEASE Program Data
Data from Alkeus’ TEASE program in Stargardt disease were presented at the 2024 American Academy of Ophthalmology annual meeting. In the TEASE-1 study, a placebo-controlled, double-masked, randomized 24-month study, gildeuretinol slowed the growth rate of atrophic retinal lesions area (square root) by 21.6% compared to untreated patients (p<0.001). A sensitivity analysis using non-transformed values demonstrated a 29.5% reduction in growth rate of atrophic lesions (p<0.001).
The growth rates of atrophic retinal lesions were 0.18 mm/year (0.87 mm²/year untransformed area) in the gildeuretinol 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). The difference was 0.36 mm²/year using non-transformed analysis (95% CI: 0.23 to 0.50).
Interim data from the TEASE-3 study showed that early-stage Stargardt disease patients treated with gildeuretinol showed no disease progression and remained asymptomatic while on therapy for between two and six years. Gildeuretinol treatment in early-stage Stargardt patients was associated with relatively stable visual acuity.
Clinical Perspective
Dr. Christine Nichols Kay of Vitreo Retinal Associates commented, "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. 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."
Gildeuretinol demonstrated a favorable safety and tolerability profile in both TEASE-1 and TEASE-3, with no adverse events related to hyper- or hypo-vitaminosis A.
About Stargardt Disease
Stargardt disease affects an estimated 30,000 to 87,000 people in the U.S. In individuals with Stargardt disease, a defective ABCA4 protein results in the accelerated dimerization of vitamin A, forming toxic by-products that irreversibly damage the retina, leading to progressive vision loss. Currently, there is no approved treatment for this condition.
About Gildeuretinol
Oral gildeuretinol acetate (ALK-001) is designed to reduce the dimerization of vitamin A without modulating the visual cycle. Preclinical studies have shown that gildeuretinol decreases vitamin A dimerization and prevents retinal degeneration and loss of visual function in animal models of Stargardt disease. Gildeuretinol has received Breakthrough Therapy, Rare Pediatric Disease, Fast Track, and Orphan Drug designations from the FDA for Stargardt disease.
