June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
A Phase 2 Double-masked, Placebo-controlled, Dose Ranging Study of Emixustat Hydrochloride (ACU-4429) in Subjects with GA Associated with Dry AMD
Author Affiliations & Notes
  • Pravin Dugel
    Retinal Consultants of Arizona, Ltd, Phoenix, AZ
  • Roger Novack
    Retina-Vitreous Associates Medical Group, Beverly Hills, CA, Beverly Hills, CA
  • Karl Csaky
    Texas Retina Associates, Dallas, TX, Dallas, TX
  • Preston Richmond
    Central Florida Retina, Orlando, FL, Orlando, FL
  • David Birch
    Retina Foundation of Southwest, Dallas, TX, Dallas, TX
  • Ryo Kubota
    Acucela Inc., Seattle, WA, Seattle, WA
  • Footnotes
    Commercial Relationships Pravin Dugel, Abbott (C), Alcon (C), Allergan (C), Artic Dx (C), Alimera Sciences (C), Acucela (C), Digisight (C), Genentech (C), LUX (C), Macusight (C), Neovista (C), ORA (C), Ophthotech (C), Regeneron (C), Thrombogenics (C); Roger Novack, Genentech (R), Acucela (F), Thrombogenics (F); Karl Csaky, Genentech (F), Acucela (C), QLT (C), Pfizer (C), Regeneron (C), Santen (C), Ophthotech (C), Thrombogenics (C); Preston Richmond, None; David Birch, Acucela (C), QLT (C), Neurotech, USA (C); Ryo Kubota, Acucela Inc. (I), Acucela Inc. (E), Acucela Inc. (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4506. doi:
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      Pravin Dugel, Roger Novack, Karl Csaky, Preston Richmond, David Birch, Ryo Kubota; A Phase 2 Double-masked, Placebo-controlled, Dose Ranging Study of Emixustat Hydrochloride (ACU-4429) in Subjects with GA Associated with Dry AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4506.

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      © ARVO (1962-2015); The Authors (2016-present)

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Emixustat HCl is a novel orally administered agent in clinical development for the treatment of geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Emixustat HCl acts as a rod visual cycle modulator by inhibiting isomerase (RPE65) activity and reducing retinal toxins (eg, A2E) that damage the RPE and overlying photoreceptors. The purpose of the study was to assess the biologic activity and safety of emixustat in subjects with GA compared with placebo. Four dose levels (2, 5, 7, and 10 mg) and 2 dose regimens (AM and PM dosing) were evaluated.


: Subjects (n=72) were randomly assigned to emixustat HCl (2, 5, 7 or 10 mg AM, or 5 mg PM) or placebo orally daily for up to 90 days in a 3:1 ratio. Adverse events and other safety parameters were collected. After 30 min of dark adaptation, ERGs were recorded, then eyes were photo bleached and ERGs were recorded immediately and at 10, 20, and 30 min. Rod b-wave amplitudes were expressed as a percentage of the prebleach dark-adapted rod amplitude from baseline. The rate of rod recovery (slope) for each emixustat HCl group was compared to the placebo group.


Emixustat HCl suppressed ERG b-wave rod recovery after light exposure in a dose-related manner. Suppression plateaued by Day 14 of dosing, and reversed within 7-14 days after cessation. No systemic adverse events (AEs) of concern were noted. Chromatopsia and delayed dark adaptation were the most common ocular AEs. There were 2 subjects with a treatment-related serious AE (both were moderate chromatopsia; at 5 mg). All ocular AEs resolved upon drug cessation; most events were mild and no severe events were observed.


This proof of concept study demonstrated a dose-dependent biologic effect and emixustat’s ability to modulate the visual cycle. Despite oral dosing, systemic adverse events were minimal. The common ocular AEs are explainable based on the understood mechanism of action. Results suggest that emixustat HCl has the potential to be a useful agent in the treatment of geographic atrophy associated with dry AMD. A long-term Phase 2b/3 study is underway to evaluate emixustat HCl in GA subjects.

ERG b-wave Rod Recovery vs Placebo - Day 14
ERG b-wave Rod Recovery vs Placebo - Day 14
Keywords: 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • 412 age-related macular degeneration • 688 retina  

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