Alkeus Pharmaceuticals has announced topline results from its SAGA trial, evaluating the investigational oral therapy gildeuretinol (ALK-001) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The double-masked, randomized, placebo-controlled trial demonstrated a statistically significant reduction in GA lesion growth rate of 15.3% versus placebo from 6 to 24 months (p=0.047). This finding suggests a potential new approach to managing this progressive and debilitating condition.
The SAGA trial's principal investigator, Alexander Melamud, MD, MA, presented the results at the 128th Annual Meeting of the American Academy of Ophthalmology. The study also indicated a slowing in GA growth rate of 13.4% from baseline to 24 months (p=0.075), which were the study’s primary endpoints.
Impact on Visual Function
Beyond anatomical changes, the study also assessed the impact of gildeuretinol on visual function. Patients treated with gildeuretinol lost 4.4 fewer letters (p=0.031) in low luminance visual acuity (LLVA) over 24 months, a key secondary endpoint. According to Dr. Melamud, "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 growth rate of GA lesions was assessed by fundus autofluorescence.
Safety and Tolerability
The safety and tolerability profile of gildeuretinol in the SAGA trial was consistent with prior clinical studies in Stargardt disease. Notably, patients at risk of developing choroidal neovascularization or wet AMD experienced fewer adverse events in the gildeuretinol group (11%) compared to the placebo group (44%).
Mechanism of Action
Seemi Khan, MD, MPH, MBA, chief medical officer of Alkeus Pharmaceuticals, explained the significance of the findings: "These data represent the first clinical demonstration that slowing vitamin A dimerization could be a target in the treatment of GA secondary to AMD. By slowing dimerization with gildeuretinol’s unique mechanism, we could reduce further damage to the retina at more advanced stages and possibly delay or prevent the onset of GA."
Expert Commentary
Charles Wykoff, MD, PhD, retina specialist and director of research at Retina Consultants of Texas, commented on the potential impact of these findings: "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."
