Emixustat hydrochloride (emixustat) is under clinical development by Acucela Inc. (Acucela) for retinal diseases including Stargardt disease (STGD). This is a rare, inherited degenerative disease of the retina affecting approximately 1 in 8,000 to 10,000 individuals and is the most common type of hereditary macular dystrophy. There are no approved treatments for STGD. Stargardt disease is characterized by an excessive build-up of lipofuscin. Lipofuscin, which normally accumulates with age, consists of lipids, proteins, and toxic bis-retinoids such as A2E. Accumulation of the bis-retinoids is thought to cause retinal pigment epithelium (RPE) cell dysfunction, which leads to photoreceptor death and loss of vision. Animal models have shown that persistent treatment with emixustat slows down the rate at which these toxins, such as A2E, accumulate. The data collected from mice with high levels of A2E suggest that the accumulation of A2E can be reversed by emixustat treatment.
Nonclinical findings suggest that, orally administered emixustat may slow the progression of STGD. This study is a multicenter, randomized, double-masked, placebo-controlled study to determine if emixustat reduces the rate of progression of macular atrophy (MA) compared to placebo in subjects with STGD. Subjects will be randomly assigned to one of two treatment arms in a 2:1 (emixustat:placebo) ratio. Subjects will self-administer orally the study drug once a day every evening for 24 months. This study will be conducted at approximately 30 sites in the US, Europe, and other countries. Approximately 162 subjects will be enrolled (108 emixustat and 54 placebo). Randomization and double-masking will be used to minimize bias in subject selection and the evaluation of subjects during the study. A placebo control is included to provide an objective comparison for the safety and efficacy of emixustat. The maximum duration of participation in the study will be 27 months, with a total of 13 visits.