Emixustat for Proliferative Diabetic Retinopathy

Our approach to Diabetic Retinopathy: Emixustat hydrochloride


Modulation of the visual cycle is a novel approach to treating Diabetic Retinopathy (DR). The retina has a higher metabolic rate in the dark than in light, using more energy and oxygen. Slowing the visual cycle with emixustat in the night-time is expected reduce the metabolic burden of the eye. This includes reducing the retina's oxygen demand, which may slow the progression of diabetic retinopathy - a condition in which decreased oxygen supply plays a significant role. Preclinical evidence supports a mechanism of action in which emixustat effectively reduces oxygen consumption under dark conditions.

Unlike current invasive treatments, emixustat is orally administered. Oral treatment would transform the therapeutic landscape, which currently encompasses laser therapy, surgery, and intravitreal injections - all invasive procedures with corresponding risks of complications. Emixustat has the potential to shift the treatment paradigm in DR.

Acucela conducted a clinical study from April 2016 until November 2017 in the U.S. The study (Protocol 4429-203) was 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 statistically significant level (difference in means of 48.1 microns favoring emixustat, p=0.0764; statistical significance pre-specified at p<0.1). 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=0.0263). Both analyses included nine patients in the emixustat group and eleven 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.