Gildeuretinol for Stargardt Secures FDA Rare Pediatric, Fast Track Status

Credit: Vitreo Retinal Associates

Gildeuretinol (ALK-001), an investigational oral therapy, has received Rare Pediatric Disease and Fast Track designations from the US Food and Drug Administration (FDA) for the treatment of Stargardt disease.¹

Announced by Alkeus Pharmaceuticals, on November 18, 2024, the company indicated its plans to apply for a Priority Review voucher with the submission of the New Drug Application (NDA) for gildeuretinol for Stargardt.

“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,” Michel Dahan, president and CEO of Alkeus, said in a statement. “These designations were granted on top of the previously awarded Breakthrough Therapy and Orphan Drug designations.”

Gildeuretinol is designed to lower the dimerization of vitamin A without affecting the visual cycle.² Data reported in the randomized, placebo-controlled, double-masked TEASE-1 trial found clinically and statistically significant slowing in lesion growth after 2 years of gildeuretinol treatment in late-stage Stargardt disease.

At the 128th Annual American Academy of Ophthalmology (AAO) Meeting, TEASE-1 data showed gildeuretinol slowed the growth rate of atrophic retinal lesions area by 21.6% compared with untreated patients.³ 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, for a mean difference of 0.05 mm/year (95% CI, 0.03 to 0.07, P <0.001).

According to interim data from the TEASE-3 study, patients with early-stage Stargardt disease had no disease progression and continued to be asymptomatic on gildeuretinol for 2 to 6 years.¹ Notably, visual acuity remained relatively stable in patients with early-stage Stargardt treated with gildeuretinol.

“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,” investigator Christine N. Kay, MD, Vitreo Retinal Associates, said in a statement.¹ “In addition, the TEASE-3 data indicate the potential value of treating patients with Stargardt disease as early as possible, before the onset of progressive central vision loss.”

Without an FDA-approved treatment, Stargardt affects approximately 30,000 to 87,000 people in the US.⁴ Gildeuretinol has previously received Breakthrough Therapy and Orphan Drug designations from the FDA.¹

“Together, these achievements recognize the significant unmet medical need in Stargardt disease and the overwhelming burden on patients as well as their families and caregivers,” Dahan added.¹

For more insight into the TEASE trials, watch a full HCPLive interview with Kay discussing the promise of gildeuretinol for Stargardt at AAO 2024.³

“It was exciting to be able to give the first randomized, controlled trial that has shown efficacy in Stargardt presentation," Kay told HCPLive.³ "This drug has orphan drug status and breakthrough designation status from the FDA, and the company is moving forward with the FDA pathway shortly, so we'll be excited to follow along and see how things go."

References

1. _{Alkeus Pharmaceuticals receives FDA rare pediatric disease and fast track designations for Gildeuretinol as a treatment for stargardt disease. Alkeus Pharmaceuticals Inc. November 18, 2024. Accessed November 22, 2024. https://alkeuspharma.com/alkeus-pharmaceuticals-receives-fda-rare-pediatric-disease-and-fast-track-designations-for-gildeuretinol-as-a-treatment-for-stargardt-disease/.}
2. _{Iapoce C. Gildeuretinol shows promise in slowing geographic atrophy progression. HCP Live. October 21, 2024. Accessed November 22, 2024. https://www.hcplive.com/view/gildeuretinol-shows-promise-in-slowing-geographic-atrophy-progression.}
3. _{Iapoce C. Christine N. Kay, MD: Tease trials show promise of gildeuretinol for stargardt. HCP Live. October 28, 2024. Accessed November 22, 2024. https://www.hcplive.com/view/christine-n-kay-md-tease-trials-show-promise-of-gildeuretinol-for-stargardt.}
4. _{Kohli P, Tripathy K, Kaur K. Stargardt Disease. [Updated 2024 Jan 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587351/}