Though Alkeus Pharmaceuticals’ oral eye disease asset failed to significantly reduce geographic atrophy (GA) lesion growth, the biotech is citing “clinically meaningful” results and a secondary endpoint win as reasons to pursue further development.
The candidate in question is gildeuretinol acetate, also called ALK-001, a form of deuterated vitamin A assessed in a phase 3 trial dubbed SAGA. The 24-month study enrolled 198 patients with GA secondary to age-related macular degeneration (AMD), a chronic eye disease that can cause vision loss.
The late-stage study failed to meet its primary efficacy endpoint, which measured the growth rate of GA lesions from baseline to 24 months using an in vivo imaging tool called Fundus Autofluorescence. A reduction of 0.25 square millimeters per year was seen at 24 months compared to placebo, a difference that wasn’t statistically significant (p=0.07), according to a Sept. 17 release.
Despite that, the data “clearly indicate a clinically meaningful trend in slowing the growth rate of GA lesions,” Alkeus chief medical officer Seemi Khan, M.D., said in the release, deeming the results “extremely encouraging.”
“The SAGA data represent the first clinical demonstration that slowing vitamin A dimerization could be beneficial in the treatment of GA secondary to AMD,” Khan said. “Results from SAGA build upon the positive data from TEASE-1, a study of gildeuretinol in Stargardt disease. We look forward to discussing these results with the U.S. Food and Drug Administration to determine the optimal path forward.”
Gildeuretinol did demonstrate a statistically significant reduction in the loss of low luminance visual acuity, a risk factor for disease progression and a secondary endpoint in the study. The candidate also showed a favorable safety and tolerability profile, a result consistent with the company’s prior clinical studies in Stargardt disease, according to Alkeus.
GA is a progressive condition that can cause irreparable central vision loss. Currently, there aren’t any oral therapies approved by the FDA for the condition.
“I am highly encouraged by the results of an oral treatment that showed a significant reduction of the growth rate of GA, as well as its effect on visual acuity,” David Boyer, M.D., principal investigator and retina specialist with Retina-Vitreous Associates Medical Group of Los Angeles, said in the company release. “The patient population afflicted with GA is in desperate need of an oral treatment to slow disease progression. I’m extremely excited by these data and believe this is a significant advancement of our scientific understanding of the GA disease mechanism.”
While the fate of the candidate remains unclear in GA, Alkeus CEO Michel Dahan said the company will continue to work “to bring oral gildeuretinol to those in need starting with individuals impacted by Stargardt disease, subject to regulatory approval.”
The asset has snagged both breakthrough therapy and orphan drug designations from the FDA in the rare genetic eye disease indication. A phase 2 study of the candidate showed statistically significant slowing of retinal lesion growth over two years among patients with late-stage Stargardt, according to Alkeus.
The Massachusetts-based biotech, backed by Bain Capital Life Sciences, is currently running additional clinical trials for gildeuretinol in Stargardt disease.