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Phase IIa trial recruits first patient for novel therapy directed towards treatment of Stargardt’s disease.

A Phase IIa human study, sponsored by Acucela Inc., based in Seattle, Washington, has announced the recruitment of its first patient to evaluate emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. The experimental small molecule treatment, a visual cycle modulator, will be tested in a multicenter, randomized, blinded study to investigate the pharmacodynamics, safety and tolerability of emixustat in Stargardt’s patients that meet the designated inclusion criteria. An estimated 30 subjects will be enrolled at clinical sites in the United States and will be randomly assigned in a 1:1:1 ratio of emixustat 2.5 mg, emixustat 5 mg, and emixustat 10 mg.  The protocol involves patients taking the study drug orally once daily for one month.


The rationale behind the mode of action of the drug is understood to rest on the principle of reducing the impact of certain stressors in the retina, including light, oxygen tension and accumulation of toxic retinoid by-products. In particular, independent research in animal models suggests that reduction of visual chromophore biosynthesis in the visual cycle could potentially prevent retinal pathology caused by stressors such as light, retinoid by-products, and oxygen. More recent clinical studies, addressing safety, tolerability, and pharmacodynamics of emixustat, found that the treatment suppressed rod photoreceptor sensitivity in a dose-dependent and reversible manner. In a previous study in an allied retinal pathology, the majority of systemic adverse events were not considered treatment related, many of which were understood to have resolved on study or within 7 to 14 days after study drug cessation.


Stargardt disease is classified as a rare genetically inherited disorder affecting the retina of young patients often leading to slow progression of vision loss. Often referred to as juvenile macular degeneration, the disorder affects approximately 1 in 10,000 individuals worldwide, in which the most common genetic lesion is in the ABCA4 gene. The disease affects < 40,000 patients in the United States. where it is designated as an orphan disease. Previously, the FDA granted orphan drug designation to emixustat for the treatment of Stargardt disease. The emuxistat treatment represents an oral non-retinoid, small molecule inhibitor of RPE65 and previous animal studies have demonstrated that emixustat could inhibit RPE65 in a dose-dependent, reversible manner. Commenting on the clinical trial recruitment milestone, Dr. Hendrik Scholl, University Hospital in Basel Switzerland stated, “This is an important therapeutic development for patients with Stargardt Disease. Emixustat addresses a well-understood mechanism that leads to toxic accumulation of material underneath the retina linked to visual loss in Stargardt disease and therefore is a promising compound for this debilitating disease.”