Date: 2016-04-19
Type of information: Completion of the trial
phase: 2b-3
Announcement: completion of patient treatment
Company: Acucela (USA - MA) Otsuka Pharmaceuticals (Japan)
Product: emixustat hydrochloride
Action
mechanism: enzyme inhibitor/RPE65 inhibitor. Emixustat hydrochloride (emixustat) is a once-daily, orally administered small molecule that inhibits RPE65, an enzyme crucial to the visual cycle, the chemical pathway in the retina central to the initiation of visual perception. Emixustat has been shown to play a critical role in slowing the progression of multiple retinal degenerative diseases in animal models, including GA secondary to AMD. Emixustat is being developed by Acucela in collaboration with Otsuka Pharmaceutical. Acucela has received fast-track designation for emixustat for the treatment of GA secondary to dry AMD by the FDA.
Disease: geographic atrophy (GA) associated with dry age-related macular degeneration (AMD)
Therapeutic area: Ophtalmological diseases
Country: USA
Trial
details: The S.E.A.T.T.L.E study compared the efficacy and safety of emixustat to placebo for the treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). A total of 508 subjects were randomized to receive emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for up to 24 months. The primary efficacy endpoint was the mean rate of change from baseline in the total area of the GA lesion(s) in the study eye as imaged by fundus autofluorescence. Secondary efficacy endpoints included the mean change from baseline in normal luminance best-corrected visual acuity score and the proportion of subjects who developed choroidal neovascularization in their study eye. Safety and tolerability were assessed on the basis of ocular and non-ocular adverse events, serious adverse events, ophthalmic examination findings, vital signs, physical examination findings, electrocardiogram findings, and laboratory analyses. (NCT01802866)
Latest
news: * On April 19, 2016, Acucela announced the completion of the treatment period in the ongoing Phase 2b/3 clinical trial, the S.E.A.T.T.L.E. study, of the investigational visual cycle modulator emixustat hydrochloride (emixustat). The study enrolled 508 patients with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). The last patient has completed the treatment period of 24 months. The primary objective of the study is to detect differences in lesion growth rate between treatment groups. Acucela expects to analyze and report top-line data from this clinical trial by June 2016. * On June 3, 2015, Acucela, a clinical-stage biotechnology company that specializes in discovering and developing novel drug candidates to potentially treat and slow the progression of sight-threatening ophthalmic diseases, announced the publication of results from a Phase 2a clinical trial of emixustat hydrochloride (emixustat) in patients with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD) in the June online edition of RETINA: The Journal of Retinal and Vitreous Diseases. The lead author on the paper is Pravin U. Dugel, MD, Managing Partner, Retinal Consultants of Arizona and Clinical Professor, USC Eye Institute, Keck School of Medicine, University of Southern California. He was also a principal investigator of the emixustat study. The published article is titled “Phase II, Randomized, Placebo-Controlled, 90-Day Study of Emixustat HCL in Geographic Atrophy Associated with Dry Age-Related Macular Degeneration ”. The study was designed to assess the safety, tolerability, and pharmacodynamics of emixustat in subjects diagnosed with GA. Seventy-two subjects were randomized to receive one of four emixustat doses (2, 5, 7, or 10 mg once daily) or placebo for a 90-day treatment period. Biologic activity of emixustat in the retina was measured by electroretinography (ERG). Safety evaluations included analysis of adverse events and ophthalmic examinations. The ERG data showed a dose-dependent pharmacologic effect of emixustat, consistent with the proposed mechanism of action. The authors noted that most systemic adverse events (AEs) observed in the clinical trial were not considered treatment related and that ocular AEs were mild to moderate in severity. The limitations of the study include its small sample size and the proportion of subjects who did not complete the entire 90-day dosing period.
