Phase 1, Dose-Ranging Study of Emixustat Hydrochloride (Acu-4429), a Novel Visual Cycle Modulator, in Healthy Volunteers

Abstract

Oral emixustat was safe and well tolerated when administered once daily for 14 days with minimal systemic adverse events reported. These data support evaluation of emixustat in subjects with geographic atrophy associated with dry age-related macular degeneration.

Molecular pharmacodynamics of emixustat in protection against retinal degeneration

“…This concept was first tested in patients treated with 13-cis-retinoic acid (isotretinoin) or its derivatives (18)(19)(20) and led to the development of an inhibitor of RPE65, the non-retinoid derivative of retinylamine (Ret-NH 2 ) emixustat (previously known as ACU-4429) (21). Currently, emixustat hydrochloride is being tested in a phase IIb/III multicenter, randomized, double-masked, dose-ranging study by comparing its efficacy and safety with placebo for the treatment of dry age-related macular degeneration (AMD) (ClinicalTrials.…”

Single Intravitreal Injection of Etamsylate for the Treatment of Geographic Atrophy Associated with Submacular Hemorrhage

“…Opposed to anti-VEFG therapy of exudative AMD, there are not any currently approved treatment for GA. Current clinical trials are investigating remedies for dry GA through multiple approaches, including inflammation, the visual cycle, neuroprotection and cell replacement therapy [9][10][11][12]. Aetiology of dry AMD suggests that the treatment of inflammation could be a suitable alternative to treat dry AMD [13].…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…Given the well-defined functional and biochemical role of the visual cycle protein RPE-specific protein 65 kDa (RPE65) , inhibitors specific to RPE65 were developed to slow the rate of retinoid metabolism to slow A2E generation (Buschini et al 2015;Zhang et al 2015). Emixustat specifically binds RPE65 at its active site to inhibit its activity (Kubota et al 2014). Later work found emixustat scavenges free retinoids as well, and that this activity heavily contributes to its mechanism-of-action .…”

“…Later work found emixustat scavenges free retinoids as well, and that this activity heavily contributes to its mechanism-of-action . Early phase I clinical trials tested the safety and tolerance of emixustat through oral administration of the drug in doses ranging from 5 to 40 mg over a 14-day period (Kubota et al 2014). Two-thirds of patients experienced mild adverse reactions to the drug, and because these adverse reactions resolved at the end of the study (Kubota et al 2014), emixustat proceeded to phase II/III clinical trial (Dugel et al 2015).…”