What you missed at AAO 2024: Gildeuretinol acetate (ALK-001)
Patients treated with investigational oral therapy gildeuretinol (ALK-001) showed a statistically significant reduction in the GA lesion growth rate.
(Image credit: AdobeStock/AI Story)
Patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) treated with investigational oral therapy gildeuretinol (ALK-001) showed a statistically significant reduction in the GA lesion growth rate of 15.3% vs. placebo from 6 to 24 months (p=0.047).1
In addition to the reduction in lesion growth, gildeuretinol also demonstrated a statistically significant visual function improvement, showing 4.4 fewer letters lost (p=0.031) in low luminance visual acuity (LLVA) over 24 months and a clinically meaningful trend in slowing GA growth rate of 13.4% from baseline to 24 months (p=0.075). This was the study’s primary endpoint. A trend toward functional benefit in best corrected visual acuity (BCVA) was demonstrated with 3.3 fewer letters lost (p=0.099).1
The SAGA trial
SAGA was a 24-month, double-masked, randomized, placebo-controlled trial to investigate the safety, pharmacokinetics, tolerability and efficacy in patients with GA secondary to AMD. The study enrolled 198 patients. The primary efficacy endpoint was the growth rate of GA lesions from baseline to 24 months as assessed by Fundus Autofluorescence (FAF). The first key secondary endpoint was the change in LLVA from baseline to 24 months.1
A favorable safety and tolerability profile was demonstrated by gildeuretinol, consistent with prior clinical studies of gildeuretinol in Stargardt disease. Additionally, 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 the retina specialist investigators.1
Experts weigh in
Charles Wykoff, MD, PhD, retina specialist and Director of Research at Retina Consultants of Texas shared his thoughts on this data in the company’s press release.1 He said, “These data are meaningful and changing the conversation in the space about what might be possible with next generation treatments for patients with GA and earlier stages of AMD. While the primary endpoint was not met, the anatomic efficacy signal appears real, and most interestingly there appears to be a consistent signal of functional preservation with treatment. This patient population could benefit tremendously from a safe and effective systemic treatment option.”
Alexander Melamud, MD, MA, retina specialist and vitreoretinal surgeon with the Retina Group of Washington and a principal investigator in the SAGA study presented the topline results of the SAGA study during the 128th Annual Meeting of the American Academy of Ophthalmology (AAO) held in Chicago.1
Melamud also spoke to this data, saying, “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. One of the first things patients lose in macular degeneration is low light vision, which can have a dramatic impact on daily living. 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.”1
Modern Retina also spoke with Christine N. Kay, MD, about the TEASE study using gildeuretinol in patients with Stargardt disease: Watch the interview
