Alkeus Pharmaceuticals' gildeuretinol (ALK-001), an investigational oral therapy, has been granted Rare Pediatric Disease and Fast Track designations by the FDA for the treatment of Stargardt disease. This decision underscores the potential of gildeuretinol to address the significant unmet medical need in this inherited retinal disease affecting approximately 30,000 to 87,000 people in the US.
Clinical Trial Data
The FDA's decision was influenced by data from the randomized, placebo-controlled, double-masked TEASE-1 trial, which demonstrated clinically and statistically significant slowing in lesion growth after 2 years of gildeuretinol treatment in late-stage Stargardt disease. Specifically, the TEASE-1 data presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting showed that gildeuretinol slowed the growth rate of atrophic retinal lesions by 21.6% compared with untreated patients. 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, resulting in 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 further supported the potential of gildeuretinol, indicating that patients with early-stage Stargardt disease experienced no disease progression and remained asymptomatic for 2 to 6 years while on gildeuretinol. Notably, visual acuity remained relatively stable in these patients.
Mechanism of Action
Gildeuretinol is designed to lower the dimerization of vitamin A without affecting the visual cycle. This mechanism is crucial in addressing the underlying pathology of Stargardt disease, where the accumulation of toxic vitamin A byproducts leads to retinal damage.
Expert Commentary
"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," said investigator Christine N. Kay, MD, Vitreo Retinal Associates. She further emphasized the potential value of treating patients with Stargardt disease as early as possible, before the onset of progressive central vision loss, based on the TEASE-3 data.
Regulatory Pathway
With the Rare Pediatric Disease and Fast Track designations, Alkeus Pharmaceuticals plans to apply for a Priority Review voucher upon submission of the New Drug Application (NDA) for gildeuretinol. These designations build upon the previously awarded Breakthrough Therapy and Orphan Drug designations, highlighting the FDA's recognition of the significant unmet medical need in Stargardt disease.
Michel Dahan, president and CEO of Alkeus, stated that these achievements recognize the overwhelming burden on patients, their families, and caregivers affected by Stargardt disease.
