Emixustat for Geographic Atrophy Secondary to AMD
Ophthalmology, October 2018
Rosenfeld et al. evaluated the use of emixustat hydrochloride in the management of geographic atrophy (GA). They found that emixustat did not reduce the growth rate of GA—and that the most common adverse events were ocular in nature and likely attributable to the drug’s mechanism of action.
Enrollees (N = 508) had GA secondary to age-related macular degeneration (AMD), total GA area ranging from 1.25 to 18 mm2, and a visual acuity score of at least 35 letters. Participants were assigned randomly (1:1:1:1) to receive placebo or emixustat (2.5, 5, or 10 mg) administered orally, once daily, for 24 months. Evaluations were conducted from screening through month 25. The primary efficacy endpoint was the mean annual growth rate of total GA area, which was measured from fundus autofluorescence images at a central reading center. Also measured was the change from baseline in normal luminance best-corrected visual acuity (NL-BCVA). Safety and tolerability were determined by documenting adverse effects, measuring vital signs, and reviewing findings from lab tests and physical exams.
The study was completed by 320 patients (63%). Demographics and baseline characteristics were comparable among the 4 groups. During the study, average GA growth rates were similar with placebo and emixustat (placebo: 1.69 mm2 per year; emixustat groups: 1.69-1.84 mm2 per year). Changes in NL-BCVA also were comparable among the study groups. Subjects whose low luminance deficit (LLD) was larger at baseline (≥20 letters) had faster GA growth during the 24-month treatment period. No meaningful association was observed between GA growth rate and the risk-allele status of the AMD-associated single-nucleotide polymorphisms that were tested.
The most common adverse events in patients treated with emixustat were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%).
The authors noted that this research sheds further light on the natural history of GA and confirms previously observed links between certain baseline traits and the rate of GA growth. Even though emixustat was not effective in their study, robust safety data were gained that may be relevant to other indications for emixustat.
The original article can be found here.