Emixustat for Stargardt Disease

Our visual cycle modulation approach to Stargardt Disease: Emixustat hydrochloride


The visual cy cle is the process by which vitamin A is recycled in the eye; vitamin A is crucial to the visual process. Emixustat modulates the visual cycle by inhibiting a critical enzyme of this pathway, Retinal pigment epithelium-specific 65 kDa protein (RPE65). Slowing the visual cycle reduces the availability of vitamin A derivatives (11-cis- and all-trans-retinal) to form precursors of A2E and related compounds. In animal models of Stargardt disease and retinal degeneration, emixustat was found to decrease the accumulation of A2E and to protect the retina from light-induced damage. Emixustat when delivered orally was found to be generally well tolerated in human clinical studies and indicated a delayed dark adaptive response in electrical retinogram, being the most common pharmacological sign of Emixustat.

On November 7, 2018, Kubota Vision initiated a phase 3 clinical study in Stargardt disease.The study is a multi-center, randomized, double-masked, and placebo-controlled phase 3 clinical study in which subjects are randomly assigned to emixustat 10 mg or placebo (2:1 ratio) once daily for 24 months. The target total number of subjects was 162; however, due to high interest in the study, a total of 194 subjects were enrolled in this study across 29 sites in 11 countries worldwide.

The primary objective of this study is to determine if emixustat reduces the rate of macular atrophy progression, in comparison to placebo, in subjects with Stargardt disease. Secondary objectives include assessing changes in visual function parameters such as BCVA (best-corrected visual acuity) letter score and reading speed.

Kubota Vision received orphan drug designation for emixustat for the treatment of Stargardt disease by FDA (U.S. Food and Drug Administration) and also by EMA (European Medicines Agency).

In August 2020, Kubota Vision announced that the FDA Office of Orphan Products Development (OOPD) has awarded an orphan products clinical trial grant to support the ongoing phase 3 study of emixustat in Stargardt disease (Clinicaltrials.gov identifier: NCT03772665).