PT - JOURNAL ARTICLE AU - Kubota, Ryo AU - Birch, David G AU - Gregory, Jeff K AU - Koester, John M TI - Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease AID - 10.1136/bjophthalmol-2020-317712 DP - 2022 Mar 01 TA - British Journal of Ophthalmology PG - 403--408 VI - 106 IP - 3 4099 - http://bjo.bmj.com/content/106/3/403.short 4100 - http://bjo.bmj.com/content/106/3/403.full SO - Br J Ophthalmol2022 Mar 01; 106 AB - Background/Aims Stargardt disease is a rare, inherited, degenerative disease of the retina that is the most common type of hereditary macular dystrophy. Currently, no approved treatments for the disease exist. The purpose of this study was to characterise the pharmacodynamics of emixustat, an orally available small molecule that targets the retinal pigment epithelium–specific 65 kDa protein (RPE65), in subjects with macular atrophy secondary to Stargardt disease.Methods In this multicentre study conducted at six study sites in the USA, 23 subjects with macular atrophy secondary to Stargardt disease were randomised to one of three doses of daily emixustat (2.5 mg, 5 mg or 10 mg) and treated for 1 month. The primary outcome was the suppression of the rod b-wave recovery rate on electroretinography after photobleaching, which is an indirect measure of RPE65 inhibition.Results Subjects who received 10 mg emixustat showed near-complete suppression of the rod b-wave amplitude recovery rate postphotobleaching (mean=91.86%, median=96.69%), whereas those who received 5 mg showed moderate suppression (mean=52.2%, median=68.0%). No effect was observed for subjects who received 2.5 mg emixustat (mean=−3.31%, median=−12.23%). The adverse event profile was consistent with prior studies in other patient populations and consisted primarily of ocular adverse events likely related to RPE65 inhibition.Conclusion This study demonstrated dose-dependent suppression of rod b-wave amplitude recovery postphotobleaching, confirming emixustat’s biological activity in patients with Stargardt disease. These findings informed dose selection for a 24-month phase 3 trial (SeaSTAR Study) that is now comparing emixustat to placebo in the treatment of Stargardt disease-associated macular atrophy.No data are available. The drug being tested in this clinical trial is investigational, and the data are proprietary and may be part of future regulatory submissions. Therefore, the data cannot be made available at this time.