Alkeus Pharmaceuticals announced topline results from its SAGA study, revealing that oral gildeuretinol (ALK-001) significantly slowed the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The investigational therapy demonstrated a statistically significant reduction in GA lesion growth rate and improved visual function. The findings, presented at the American Academy of Ophthalmology (AAO) meeting, suggest a potential new approach to treating this debilitating condition.
SAGA Study Results
The SAGA trial, a 24-month, double-masked, randomized, placebo-controlled study, involved 198 patients with GA secondary to AMD. The primary endpoint was the growth rate of GA lesions from baseline to 24 months, assessed by Fundus Autofluorescence (FAF). While the primary endpoint showed a clinically meaningful trend (p=0.075), a pre-specified sensitivity analysis revealed a statistically significant 15.3% reduction in lesion growth rate from 6 to 24 months (p=0.047) in the gildeuretinol group compared to placebo.
Gildeuretinol also demonstrated a statistically significant improvement in low luminance visual acuity (LLVA), a key secondary endpoint, with patients losing 4.4 fewer letters compared to the placebo group (p=0.031) over 24 months. There was also a trend toward functional benefit in best corrected visual acuity (BCVA) with 3.3 fewer letters lost (p=0.099).
Mechanism of Action and Clinical Significance
Gildeuretinol is designed to reduce the dimerization of vitamin A, a process implicated in the formation of lipofuscin and subsequent retinal pigment epithelium and photoreceptor degeneration. By slowing vitamin A dimerization, gildeuretinol aims to reduce disease progression and slow lesion growth rate in GA related to AMD.
"These data indicate a significant slowing of the growth rate of GA lesions, as well as reducing visual function decline," said Seemi Khan, M.D., M.P.H., M.B.A., Chief Medical Officer of Alkeus Pharmaceuticals. "These data represent the first clinical demonstration that slowing vitamin A dimerization could be a target in the treatment of GA secondary to AMD."
Safety and Tolerability
Gildeuretinol demonstrated a favorable safety and tolerability profile, consistent with previous clinical studies in Stargardt disease. Notably, among participants at risk of developing Choroidal Neovascularization (CNV) or wet AMD, only 11% in the gildeuretinol group experienced these adverse events compared to 44% in the placebo group, as reported by clinical investigators.
The Unmet Need in Geographic Atrophy
GA is a progressive condition leading to irreversible central vision loss, affecting over 1 million people in the United States, with 160,000 new cases each year. Currently, there is no FDA-approved oral therapy for GA, highlighting the significant unmet medical need.
"One of the most exciting aspects of these results is that gildeuretinol is the first oral medication to show a meaningful positive effect on low luminance visual acuity in macular degeneration," said Alexander Melamud, M.D., M.A., retina specialist and vitreoretinal surgeon with the Retina Group of Washington and a principal investigator in the SAGA study. "The positive effect demonstrated on LLVA is significant. Based on these results, this therapy would definitely have a place in the overall strategy of treating AMD and slowing the decline observed in our patients. The favorable safety profile could warrant treatment as early as possible."
