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.
- clinical trial
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Contributors All authors contributed to the research design of the study, the analysis and interpretation of the study results, and the revision and review of the manuscript. JG contributed to study administration and supervision, and JMK contributed to the data analysis. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding Funding for the study was provided solely by Kubota Vision. This study was registered with ClinicalTrials.gov as NCT03033108.
Competing interests RK, JKG and JMK are employees of Kubota Vision. RK has pending and issued patents related to emixustat hydrochloride. DGB received grants from Kubota Vision during the conduct of the study.
Patient consent for publication Not required.
Ethics approval The protocol and informed consent forms were prospectively approved by either a central institutional review board (IRB; Chesapeake IRB) or site-specific IRBs (University of Utah IRB, Johns Hopkins University School of Medicine IRB, and the Cleveland Clinic IRB).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement 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.
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