Alkeus Pharmaceuticals, Inc. reported additional findings from the phase 3 SAGA clinical trial evaluating oral gildeuretinol acetate (ALK-001) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
The data was presented during the 2025 Association for Research in Vision and Ophthalmology (ARVO) annual meeting this week in Salt Lake City, Utah.
First order of business: this candidate.
As the late-stage biopharmaceutical’s lead therapeutic, gildeuretinol acetate is a modified form of Vitamin A in which hydrogen atoms are replaced with deuterium.
Why Vitamin A?
This nutrient is key to permitting photoreceptors in the eye to convert light into electrical signals sent to the brain—enabling vision.
However: In some cases, Vitamin A can form clumps (dimers) that build up and become toxic to the retinal pigment epithelium (RPE).
- As such: These Vitamin A dimers may lead to vision loss, particularly in degenerative retinal diseases such as GA and Stargardt disease—two potential indications gildeuretinol is under clinical investigation for.
Got it. Now back to gildeuretinol and its modification.
The therapeutic is intended to slow down Vitamin A dimerization—where two molecules join to form a new compound—without any vision disruptions.
How it does this: By substituting Vitamin A (all the while training its functions) and reducing the production of those aforementioned toxic byproducts.
- The ideal outcome: Preserved retinal health and vision.
- And the potential result: Preventing the onset or delaying progression of retinal diseases.
And how is this administered?
Orally—just once a day.
Now to its clinical performance.
While also undergoing clinical investigation via the TEASE clinical program for Stargardt—for which it has received four FDA designation statuses—gildeuretinol has been studied as a potential first-ever treatment for GA secondary to AMD via the phase 3 Study of ALK-001 in Geographic Atrophy (SAGA) trial.
A few details to know:
- The design: Double-masked, multicenter, randomized, placebo-controlled study (NCT03845582)
- The participants: 198 patients (aged ≥60) diagnosed with GA secondary to dry AMD in at least one eye
- The setup: Patients randomized into two dosing groups to orally receive either:
- Gildeuretinol once daily for 24 months (n = 135)
- Note: 94 of these patients completed the study
- Placebo capsule once daily for 24 months (n = 63)
- Note: 43 of these patients completed the study
- Gildeuretinol once daily for 24 months (n = 135)
And the measured outcomes?
Measured from baseline to 24 months, these included:
- Primary: Mean growth rate of GA lesions, as determined via fundus autofluorescence (FAF)
- Secondary:
- Safety and tolerability (adverse events [AEs], in other words)
- Pharmacokinetics (plasma concentrations of ALK-001 and metabolites)
- Incidence of choroidal neovascularization (CNV)
- Changes in visual acuity (VA)
- Best-corrected visual acuity (BCVA)
- Low-luminance visual acuity (LLVA)
- Changes in reading speed
- Functional reading independence (FRI)
- Visual Function Questionnaire-25 (VFQ-25)
- Reading speed
Before we get to that additional data, what did prior data find?
As reported in September 2024, gildeuretinol demonstrated a “clinically meaningful reduction” in GA lesion growth at the 24-month point as well as favorable safety and tolerability. However: The observed reduction was notably not “statistically significant”—indicating that the study failed to meet its primary endpoint.
- See here for the full rundown.
So does the new data redeem gildeuretinol’s past performance?
See for yourself:
In regards to the primary endpoint: From baseline to the 24-month visit, gildeuretinol-treated patients’ lesion growth rate declined 13.4% versus placebo (p = 0.075).
- Alkeus referred to this rate reduction as a “clinically meaningful trend.”
As for a sensitivity analysis: From months 6 to 24, gildeuretinol-treated patients’ lesion growth rate declined 15.3% versus placebo (p = 0.047).
- This reduction was noted as “statistically significant.”
And how did visual function fare among these patients?
For this secondary endpoint: Statistically significant improvements were observed as well, with gildeuretinol showing 4.4 fewer letters lost (p = 0.031) in LLVA over the 24-month period.
- Investigators emphasized that this is the first investigational oral therapy to demonstrate such LLVA visual function benefit.
Per Alkeus, this trend continued for BCVA, with 3.3 fewer letters lost (p = 0.099)—notably, another key secondary endpoint.
Sounds promising … but were there any adverse events?
Yes; however, the majority of these were mild or moderate, with gildeuretinol’s safety profile reporting no demonstrations of:
- Delayed dark adaptation
- Chromatopoisa
- Vasculitis
So what does this mean for the therapeutic?
This data—coupled with other recently-reported positive findings from the TEASE-1 trial in favor of a Stargardt indication—support continued clinical evaluation on gildeuretinol as potential systemic treatment for GA secondary to AMD.
How gildeuretinol performed for Stargardt: Daily oral gildeuretinol significantly slowed the growth of atrophic retinal lesions in Stargardt disease by 21.6% compared to the untreated group (p<0.001).
And moving forward?
Even greater headway has been made for the therapeutic’s Stargardt indication, as it has already received those key designations—Fast Track, Orphan Drug, Breakthrough Therapy, and Rare Pediatric Disease—as part of the FDA’s expedited clinical development program.
- Stay tuned for updates on Alkeus’ gildeuretinol unique mechanism and clinical journey.