Oral treatment aims to reduce GA progression by slowing vitamin A dimerization
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CHICAGO — Decreasing vitamin A dimerization may be a promising treatment avenue for treating geographic atrophy, according to a speaker here.
In his presentation at Retina Subspecialty Day at the American Academy of Ophthalmology meeting, Alexander Melamud, MD, unveiled topline results from the phase 3 SAGA study investigating the efficacy, safety and pharmacokinetics of oral gildeuretinol (Alkeus Pharmaceuticals), a form of deuterated vitamin A, in patients with GA.
Image: Anthony DeFino | Healio
“Vitamin A dimerization has been implicated in the formation of lipofuscin and [retinal pigment epithelium] and photoreceptor degeneration,” Melamud said. “Therefore, it is our hypothesis that by slowing vitamin A dimerization with gildeuretinol, we can reduce disease progression and slow lesion growth rate in geographic atrophy related to [age-related macular degeneration].”
The randomized, double-masked, placebo-controlled study assigned a total of 198 patients to treatment with gildeuretinol (135 patients) or placebo (63 patients), 70% of whom completed the study. The primary efficacy endpoint was the rate of lesion growth at 24 months, with secondary endpoints including low-luminance visual acuity and best corrected VA.
Overall, lesion growth rate reduction was not statistically significant. (P = .075).
“However, we do see a separation of effects starting at month 6 and reaching a 13.4% growth rate reduction in the gildeuretinol group as compared to placebo at final follow-up,” Melamud said.
In addition, a pre-specified sensitivity analysis demonstrated a statistically significant 15.3% reduction in lesion growth rate from 6 to 24 months (P = .047).
Patients treated with gildeuretinol also saw a reduced loss of vision compared with those in the placebo cohort, with 4.4 fewer ETDRS letters lost overall (P = .031).
“This was statistically significant,” Melamud said. “Of note, this is the first oral therapy to demonstrate improvement or stabilization on low-luminance visual acuity.”
Most treatment emergent adverse events were mild or moderate and there were no reported deaths, reinforcing a positive safety profile for gildeuretinol.
“Decreasing vitamin A dimerization is a potential mechanism of action to treat geographic atrophy,” Melamud concluded. “Compared to placebo, we see that there is a trend towards slower GA lesion growth in baseline to month 24, a statistically significant, slower GA lesion growth rate from 6 to 24 months, and statistically significant functional vision benefit on low-luminance visual acuity. This is the first investigational oral agent to demonstrate this.”
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Melamud A. Gildeuretinol in geographic atrophy: Results from SAGA, a 2-year, randomized, double-masked, placebo-controlled Study. Presented at: American Academy of Ophthalmology meeting; Oct. 18-21, 2024; Chicago.
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