Phase ii, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular degeneration

Retina. 2015 Jun;35(6):1173-83. doi: 10.1097/IAE.0000000000000606.


Purpose: This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy associated with dry age-related macular degeneration.

Methods: Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity after a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events and ophthalmic examinations.

Results: Seventy-two subjects (54 emixustat and 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14 and was reversible within 7 days to 14 days after drug cessation. Most systemic adverse events were not considered treatment related. Dose-related ocular adverse events (chromatopsia, 57% emixustat vs. 17% placebo and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate in severity, and the majority resolved on study or within 7 days to 14 days after study drug cessation. Reversibility of these adverse events with long-term administration, however, is undetermined.

Conclusion: In this Phase II study, emixustat produced a dose-dependent reversible effect on rod function that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of geographic atrophy associated with dry age-related macular degeneration.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Dark Adaptation
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electroretinography
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology
  • Female
  • Geographic Atrophy / drug therapy*
  • Geographic Atrophy / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Phenyl Ethers / administration & dosage*
  • Phenyl Ethers / adverse effects
  • Phenyl Ethers / pharmacology
  • Propanolamines / administration & dosage*
  • Propanolamines / adverse effects
  • Propanolamines / pharmacology
  • Retinal Rod Photoreceptor Cells / physiology*
  • Visual Acuity / physiology
  • cis-trans-Isomerases / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Phenyl Ethers
  • Propanolamines
  • emixustat
  • retinoid isomerohydrolase
  • cis-trans-Isomerases