FDA Grants Rare Pediatric Disease, Fast Track Designations to Gildeuretinol for Stargardt Disease Treatment

The FDA announced that oral gildeuretinol acetate (ALK-001; Alkeus Pharmaceuticals), an investigational oral therapy, has received rare pediatric disease and fast track designations for the treatment of Stargardt disease, a rare and serious pediatric disease for which no treatments currently exist.¹

Stargardt disease can cause vision problems in pediatric patients. | Image Credit: © Anastassiya | stock.adobe.com

These designations reflect positive data from Alkeus’ TEASE program in Stargardt disease that was recently presented during the 2024 American Academy of Ophthalmology annual meeting by Christine Nichols Kay, MD, in Gainesville, Florida.^1,2

In the TEASE-1 trial, a placebo-controlled, double-masked, randomized 24-month study in patients with Stargardt disease, gildeuretinol slowed the growth rate of atrophic retinal lesions area (square root) by 21.6% compared with untreated patients. Furthermore, gildeuretinol demonstrated a 29.5% reduction in growth rate of atrophic lesions in a sensitivity analysis using non-transformed values, according to the news release.¹

“Importantly, the safety profile was also excellent. There were no reports of dark adaptation or night-blindness or any significant lab issues with these patients,” Kay said in an interview following her presentation.²

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. Using non-transformed analysis, the difference was 0.36 mm²/year (95% CI, 0.23-0.50; p < .001).¹

Kay also presented interim data from the TEASE-3 study, which demonstrates 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. Additionally, treatment in early-stage Stargardt patients was associated with relatively stable visual acuity. A favorable safety and tolerability profile was demonstrated in both TEASE-1 and TEASE-3.^1,2

“TEASE-1 is the first randomized, controlled trial in Stargardt disease that has shown an efficacy end point, which is very exciting as an inherited retinal disease specialist taking care of patients with this devastating condition,” Kay said in a news release. “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.”¹

Stargardt disease is serious vision impairment in children and young adults. An estimated 30,000 to 87,000 people are affected in the US, and there is no currently approved treatment. In patients with Stargardt disease, a central blind spot is developed due to the ABCA4 protein being defective, which results in the accelerated dimerization of vitamin A and the formation of irreversible damage to the retina.^1,2

“These patients first start with a central blind spot in their macula, which is the central spot of their retina, and they develop this atrophic lesion atrophy, meaning areas that have degenerated, and this expands over time,” Kay explained.²

Gildeuretinol is designed to reduce vitamin A dimerization without modulating a patient’s visual cycle. Preclinical studies have indicated that gildeuretinol can decrease vitamin D dimerization to a normal rate while preventing retinal degeneration and loss of vision in animals with Stargardt disease.¹

Additional clinical trials are ongoing to further assess the benefit of the drug in patients with Stargardt disease. TEASE-2 and TEASE-4 comprise the rest of the TEASE program.¹

REFERENCES

1. Alkeus Pharmaceuticals. Alkeus Pharmaceuticals receives FDA rare pediatric disease and fast track designations for gildeuretinol as a treatment for Stargardt disease. News Release. Released November 18, 2024. Accessed November 20, 2024. https://www.globenewswire.com/news-release/2024/11/18/2982878/0/en/Alkeus-Pharmaceuticals-Receives-FDA-Rare-Pediatric-Disease-and-Fast-Track-Designations-for-Gildeuretinol-as-a-Treatment-for-Stargardt-Disease.html

2. Crago SM, Harp MD. AAO 2024: Gildeuretinol and Stargardt disease: The TEASE program. Ophthalmology Times. Published October 20, 2024. Accessed November 20, 2024. https://www.ophthalmologytimes.com/view/aao-2024-gildeuretinol-and-stargardt-disease-the-tease-program