A Comprehensive Monograph on the Investigational HCV NS5A Inhibitor Odalasvir (DB13041)

Executive Summary

Odalasvir (DrugBank ID: DB13041) is an investigational small molecule antiviral agent that emerged as a highly potent, second-generation inhibitor of the Hepatitis C Virus (HCV) Nonstructural Protein 5A (NS5A). Developed initially by Achillion Pharmaceuticals and later in collaboration with Janssen, Odalasvir was engineered to overcome the limitations of first-generation NS5A inhibitors, demonstrating picomolar potency against a broad spectrum of HCV genotypes and, critically, retaining activity against common resistance-associated variants (RAVs).[1] Its pharmacological profile is characterized by a remarkably long terminal elimination half-life of approximately 250 hours, supporting a convenient once-daily dosing regimen.[2]

The clinical development program for Odalasvir focused on its use within a triple direct-acting antiviral (DAA) combination regimen, JNJ-4178, which also included the HCV NS5B polymerase inhibitor adafosbuvir (AL-335) and the NS3/4A protease inhibitor simeprevir. The cornerstone of its clinical evaluation, the Phase IIb OMEGA-1 trial (NCT02765490), yielded exceptional results. In a diverse population of patients with HCV genotypes 1, 2, 4, 5, or 6, the regimen achieved Sustained Virologic Response rates 12 weeks post-treatment (SVR12) of 98.9% with a 6-week course and 97.8% with an 8-week course.[3] These outcomes, achieved with remarkably short treatment durations, were accompanied by a favorable safety and tolerability profile, with most adverse events being mild and no treatment-related serious adverse events reported.[1]