A Comprehensive Monograph on Amenamevir (DB11701)

1.0 Introduction: A New Paradigm in Anti-Herpesvirus Therapy

Amenamevir represents a significant advancement in the therapeutic landscape for infections caused by human alphaherpesviruses, specifically Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV). It is a first-in-class, non-nucleoside antiviral agent that functions as a helicase-primase inhibitor (HPI), a novel mechanism of action that distinguishes it from the long-standing standard of care.[1] For decades, the primary treatment for these common viral infections has relied on nucleoside analogues, such as acyclovir and its prodrug valacyclovir, which target the viral DNA polymerase.[3] While effective, these agents are associated with two key clinical challenges: the emergence of drug-resistant viral strains and the requirement for frequent daily dosing, which can impede patient adherence.[4]

The development of new antiherpetic drugs with alternative mechanisms of action has been a clinical priority, driven largely by the increasing prevalence of viral strains resistant to traditional DNA polymerase inhibitors. This issue is particularly acute in immunocompromised patient populations, where prolonged viral replication can lead to the selection of resistant mutants.[2] Amenamevir's novel mechanism directly addresses this unmet need, as it targets a different and essential step in the viral replication cycle, thereby retaining its efficacy against common acyclovir-resistant HSV isolates.[6]