Skip to content

Phase II clinical study of emixustat hydrochloride for treatment of geographic atrophy shows dose-dependent effect

A Phase II a human study led by retinal clinicians at the Retinal Consultants of Arizona in Phoenix, and sponsored by Acucela Inc., based in Seattle, Washington, has shown a dose-dependent response in patients receiving oral administration of emixustat hydrochloride over a 90-day period. The novel experimental small molecule treatment is a visual cycle modulator, potentially capable of addressing geographic atrophy associated with dry age-related macular degeneration. Results of the study have been published in the journal Retina, Vol. 35, Iss. 6, pp1 1173-1183.


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. The more recent clinical study was aimed at addressing the safety, tolerability, and pharmacodynamics of emixustat by randomising subjects to one of five different tretment groups: placebo, 2mg, 5mg, 7mg and 10mg oral emixustat for a period of 90 days. The research group then measured recovery of rod photoreceptor sensitivity using electroretinography (ERG) after photobleach. Of the seventy-two subjects tested (54 emixustat and 18 placebo) emixustat was found to suppress rod photoreceptor sensitivity in a dose-dependent manner plateauing by day 14 and reversible within 7 day to 14 days after drug cessation. According to the published results, most of the systemic adverse events were not considered treatment related, the majority of which were understood to resolve on study or within 7 days to 14 days after study drug cessation. However, the supporting company, Acucela, did point out that the limitations of the study included its small sample size and the proportion of subjects who did not complete the entire 90-day dosing period.


Acucela are understod to be interested in the pathological effects of photooxidative stress, retinoid byproducts and hypoxia, suspected to be prominent mediators of photoreceptor damage and degeneration in human retinal diseases, including age-related macular degeneration, Stargardt disease, proliferative diabetic retinopathy, and diabetic macular edema. Emuxistat represents an oral non-retinoid, small molecule inhibitor of RPE65 and previous animal studies demonstrated that emixustat could inhibit RPE65 in a dose-dependent, reversible manner. According to further information provided by Acucela, emixustat represents the company’s first internally developed compound with which they hope to secure regulatory approval for the treatment of geographic atrophy associated with dry AMD, subject to completion of a Phase III study.