SAGA: Oral Gildeuretinol Achieves Meaningful Reduction in GA Growth Rate

Oral gildeuretinol acetate (ALK-001) demonstrated a clinically meaningful reduction in geographic atrophy (GA) lesion growth at 24 months in patients with GA secondary to age-related macular degeneration (AMD).¹

Announced by Alkeus Pharmaceuticals, on September 17, 2024, gildeuretinol also achieved a statistically significant slowing of low-luminance visual acuity (LLVA) decline at 24 months, a key secondary endpoint, with a favorable safety and tolerability profile in patients with GA.

Topline data from the Phase 3 SAGA trial will be presented as a late-breaking abstract at the 128th Meeting of the American Academy of Ophthalmology (AAO) in Chicago next month.

“I am highly encouraged by the results of an oral treatment that showed a significant reduction of the growth rate of GA, as well as its effect on visual acuity,” said David S. Boyer, MD, a prinicipal investigator in SAGA and a retina specialist with the Retina-Vitreous Associates Medical Group of Los Angeles.¹ “The patient population afflicted with GA is in desparate need of an oral treatment to slow disease progression.”

GA is linked to irreversible loss of central vision, with an estimated mean time of nearly 6 years before patients progress to legal blindness.² Currently, no oral therapy is approved by the US Food and Drug Administration (FDA) to treat GA—nearly 1 million people in the US are affected by GA, with approximately 160,000 new cases reported each year.

Gildeuretinol is a novel molecule created as a specialized form of deuterated Vitamin A and designed to lower the dimerization of Vitamin A without disrupting vision.¹

SAGA was a double-masked, randomized, placebo-controlled trial designed to assess the safety, pharmacokinetics, tolerability, and efficacy of gildeuretinol in patients with GA secondary to AMD over 24 months. Overall, 198 patients were enrolled, with the primary endpoint defined as the growth rate in GA lesions from baseline as determined by fundus autofluorescence (FAF).

Upon analysis, gildeuretinol reduced GA lesion growth rate by 0.25 sqmm/year at 24 months compared with placebo (P = .07). The novel molecule also achieved a statistically significant reduction in the loss of LLVA at 24 months (P = .03). Its safety profile remained in line with previous studies of gildeuretinol in Stargardt disease.

“These data indicate a clinically meaningful trend in slowing the growth rate of GA lesions, which is extremely encouraging,” said Seem Khan, MD, MPH, MBA, chief medical officer of Alkeus. “The SAGA data represent the first clinical demonstration that slowing vitamin A dimerization could be beneficial in the treatment of GA secondary to AMD.”

Gildeuretinol has previously received the FDA’s Breakthrough Therapy Designation and Orphan Drug Designation for Stargardt disease. Clinically meaningful slowing of retinal lesion growth was achieved in patients with Stargardt treated with gildeuretinol over 2 years in the randomized, placebo-controlled, double-masked TEASE-1 trial.

“Results from SAGA build upon the positive data from TEASE-1, a study of gildeuretinol in Stargardt disease,” Khan added. “We look forward to discussing these results with the US Food and Drug Administration to determine the optimal path forward.”

Khan recently joined Veeral Sheth, MD, director of clinical research at University Retina, on HCPLive Ophthalmology’s flagship podcast New Insight to discuss gildeuretinol for Stargardt disease and GA, and the TEASE clinical trial program.³

References

1. _{Alkeus Pharmaceuticals announces results from the saga study of Oral Gildeuretinol in patients with geographic atrophy secondary to age-related macular degeneration. Alkeus Pharmaceuticals Inc. September 17, 2024. Accessed September 17, 2024. https://alkeuspharma.com/alkeus-pharmaceuticals-announces-results-from-the-saga-study-of-oral-gildeuretinol-in-patients-with-geographic-atrophy-secondary-to-age-related-macular-degeneration/.}
2. _{Bakri SJ, Bektas M, Sharp D, Luo R, Sarda SP, Khan S. Geographic atrophy: Mechanism of disease, pathophysiology, and role of the complement system. J Manag Care Spec Pharm. 2023;29(5-a Suppl):S2-S11. doi:10.18553/jmcp.2023.29.5-a.s2}
3. _{Iapoce C. New insight: A look at gildeuretinol (ALK-001) for stargardt disease W/ Seemi Khan, MD. HCP Live. July 2, 2024. Accessed September 17, 2024. https://www.hcplive.com/view/new-insight-look-gildeuretinol-alk-001-stargardt-disease-seemi-khan-md.}