Pharmacological profiles and clinical effects of amenamevir tablet as treatments for herpes zoster

Abstract

Herpes zoster is a viral infectious disease caused by reactivation of varicella zoster virus (VZV) in a latently infected ganglion, and is characterized by blistering and pain developing in a zonal region innervated from the ganglion. Amenamevir is an antiherpes agent that does not have a nucleic acid-like structure, and exerts antiviral action by inhibiting the enzymatic activity of a virus-derived helicase-primase complex, which is considered essential for viral DNA replication. Amenamevir is mainly metabolized by CYP3A, and excreted into feces. In in vitro antiviral testing, amenamevir demonstrated higher antiviral activity against ZV than aciclovir, and its antiviral activity did not diminish even against acyclovir-resistant VZV. In a phase III clinical study in patients with herpes zoster in Japan, cessation of new rash formation by the 4th day of administration, the primary endpoint of the study, was observed in 81.1% of the patients given oral administration of amenamevir 400 mg once daily after meal, verifying its non-inferiority to valaciclovir hydrochloride (P<0.0001 by non-inferiority test using Farrington-Manning test extended to Mantel-Haenszel type adjustment). Adverse reactions were observed in 10.0% (25/249 patients), and were mainly abnormal clinical laboratory tests results. Based on the above results, the efficacy and safety of amenamevir tablet 400 mg once daily administration in herpes zoster treatment have been confirmed, and amenamevir can be a novel treatment option in Japan.