A Comprehensive Monograph on Beclabuvir (BMS-791325): From Discovery to Clinical Application and Market Realignment

Executive Summary

Beclabuvir, also known by its research code BMS-791325, is a potent, small-molecule, non-nucleoside inhibitor of the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase. Developed by Bristol-Myers Squibb, it represents a significant achievement in medicinal chemistry, designed to allosterically inhibit viral replication by binding to the enzyme's "Thumb 1" pocket.[1] Beclabuvir's primary role in clinical practice was as a core component of an all-oral, interferon-free, fixed-dose combination (FDC) therapy. This regimen, known as DCV-TRIO, combined beclabuvir with daclatasvir, an NS5A replication complex inhibitor, and asunaprevir, an NS3/4A protease inhibitor.[3]

The clinical development program for the DCV-TRIO regimen demonstrated high rates of sustained virologic response (SVR), the benchmark for HCV cure. In pivotal Phase 3 trials (the UNITY program), the combination achieved SVR rates exceeding 90% in patients with HCV genotype 1, including those with compensated cirrhosis and those who had previously failed interferon-based therapy.[5] These robust efficacy data led to the regulatory approval of the FDC in Japan in 2016 under the trade name Ximency®, where HCV genotype 1b—a subtype against which the regimen is particularly effective—is predominant.[7]