Acucela has announced positive new clinical data on the effect of emixustat hydrochloride on retinal thickness in diabetic retinopathy (DR), a key secondary endpoint in a phase 2 study. The announcement did not address the primary endpoint, which is the change in aqueous humor concentration in eight specific biomarkers. However, in response to a question regarding findings relating to the primary endpoint, Acucela provided the following response: “Following 3 months of once-daily treatment, there were numerical differences favoring emixustat over placebo in the change-from-baseline aqueous humor concentrations of vascular endothelial growth factor. However, these changes were not statistically significant.” 
The study (protocol 4429-203) is a randomized, placebo-controlled, phase 2 clinical trial exploring the effect of oral emixustat hydrochloride in a proliferative diabetic retinopathy (PDR) population with and without macular edema. Twenty-four subjects were enrolled in the study, in which subjects in the emixustat group were titrated to their maximum tolerated dose of up to 40 mg per day. Beyond the initial assessment of the primary endpoint, a key secondary objective was to evaluate the effects of emixustat on the change in central subfield (retinal) thickness as assessed by spectral domain optical coherence tomography (SD-OCT) from baseline to day 85.

The study results indicate that the emixustat group experienced a reduction in central subfield thickness when compared to placebo at a statistical significant level (difference in means of 48.1 microns favoring emixustat, P=.0764; statistical significance prespecified at P<.1). Additionally, the emixustat group experienced a reduction in total macular volume in the study eye compared to placebo that also met statistical significance (difference in means of 0.361 mm³ favoring emixustat, P=.0263). Both prespecified analyses included 9 patients in the emixustat group and 11 patients in the placebo group.

These results illustrate the potential for emixustat to decrease retinal thickness in patients with DR. From these phase 2 findings, Acucela is preparing to advance the clinical program and is actively discussing research partnerships prior to the planned regulatory approval studies.

“We are thrilled to see these results for emixustat in the diabetic retinopathy population and are excited to advance the program,” Ryo Kubota, MD, PhD, Chairman, President and CEO of Acucela, said in a company news release. “This proof of concept is exciting as it not only addresses an important unmet need but does so through oral administration, a first for the industry. We are now focused on securing the right strategic partner as we finalize our plans to advance our clinical program.”