Gildeuretinol Halts Stargardt Progression in Interim TEASE-3 Results

Michel Dahan

Credit: Alkeus Pharmaceuticals

Positive interim data from the TEASE-3 clinical trial found once-daily oral gildeuretinol halted disease progression in additional patients with early-stage Stargardt disease, stabilizing visual acuity over multiple years.¹

Announced by Alkeus Pharmaceuticals on January 9, 2025, these 2 patients recently completed 24 months of gildeuretinol treatment, remaining consistent with prior trial results, and bringing the total to 5 patients who completed TEASE-3.

“These are extremely encouraging results that provide increased understanding of gildeuretinol’s potential to preserve sight,” Seemi Khan, MD, MBA, chief medical officer at Alkeus, said in a statement. “It is challenging to identify and enroll early-stage patients before they develop symptoms, and we are grateful to these patients and their families for participating in this study.”

Without a US Food and Drug Administration (FDA) approved treatment, defects in the ABCA4 protein in Stargardt disease result in the accumulation of vitamin A dimers that irreversibly damage the retina.² Oral gildeuretinol acetate is a molecule designed to reduce the dimerization of vitamin A without modifying the visual cycle.¹ The TEASE clinical trial program comprised 4 independent studies investigating oral gildeuretinol in Stargardt, including TEASE-1, TEASE-2, TEASE-3, and TEASE-4.

Results from the randomized, double-masked, placebo-controlled TEASE-1 trial showed that gildeuretinol achieved its prespecified primary efficacy endpoint in 50 patients with Stargardt.³ Gildeuretinol was linked to a 21.6% reduction in the growth rate of retinal atrophic lesion area (P <.001) and a 29.5% reduction for untransformed areas of retinal atrophic lesions versus intreated patients while remaining well-tolerated.

TEASE-3 marked the first early-stage clinical trial in Stargardt, an open-label study of oral gildeuretinol in patients with genetically confirmed disease and early disease signs visible on retinal imaging, but who have not yet exhibited vision loss symptoms. The trial has enrolled 7 patients to date.

In TEASE-3, fundus autofluorescence (FAF) imaging was used to determine how gildeuretinol impacted the progression of Stargardt over time, with a primary endpoint of progression after the first 2 treatment years. Among the 2 patients who now completed 24 months of treatment, once-daily oral gildeuretinol prevented disease progression and stabilized vision with a consistent, tolerable safety profile.

Among the 3 participants with Stargardt who completed TEASE-3, and remained on gildeuretinol treatment over multiple years, Alkeus reported a lack of disease progression, with the longest duration of therapy continuing for more than 7 years. Further topline data is expected in 2025 from the TEASE-2 trial, an ongoing, fully-enrolled, randomized, double-masked, placebo-controlled trial in 80 patients with moderate Stargardt disease.

Alkeus also announced plans to urgently submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) in 2025.¹ Gildeuretinol has already received Breakthrough Therapy, Rare Pediatric Disease, Fast Track, and Orphan Drug designations for Stargardt disease from the FDA.⁴

“With no approved treatment currently available, there is an urgent need to bring an option to patients,” Michel Dahan, president and chief executive officer of Alkeus, added in a statement.¹ “We plan to submit an NDA to the FDA for gildeuretinol as a treatment for Stargardt disease as soon as possible in 2025 based on compelling data generated to date from our multi-study clinical program.”

References

1. _{Alkeus Pharmaceuticals announces new positive interim tease-3 study results showing gildeuretinol prevented disease progression in early-stage stargardt patients. Alkeus Pharmaceuticals Inc. January 9, 2025. Accessed January 9, 2025. https://alkeuspharma.com/alkeus-pharmaceuticals-announces-new-positive-interim-tease-3-study-results-showing-gildeuretinol-prevented-disease-progression-in-early-stage-stargardt-patients/.}
2. _{Wang L, Shah SM, Mangwani-Mordani S, Gregori NZ. Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease. J Clin Med. 2023;12(19):6229. Published 2023 Sep 27. doi:10.3390/jcm12196229}
3. _{Iapoce C. Christine N. Kay, MD: Results of tease-1 study on stargardt disease. HCP Live. November 17, 2023. Accessed January 9, 2025. https://www.hcplive.com/view/christine-n-kay-md-results-tease-1-study-stargardt-disease.}
4. _{Iapoce C. Gildeuretinol for Stargardt secures FDA rare pediatric, fast track status. HCP Live. November 27, 2024. Accessed January 9, 2025. https://www.hcplive.com/view/gildeuretinol-for-stargardt-secures-fda-rare-pediatric-fast-track-status.}