A Comprehensive Clinical Monograph on Sofosbuvir/Velpatasvir (Epclusa) for the Treatment of Chronic Hepatitis C Virus Infection

Executive Summary

Sofosbuvir/velpatasvir, marketed under the brand name Epclusa, is a fixed-dose, single-tablet, pangenotypic, direct-acting antiviral (DAA) regimen that has fundamentally altered the therapeutic landscape for chronic Hepatitis C Virus (HCV) infection.[1] Its development and approval represent a paradigm shift, offering a simplified, highly effective, and well-tolerated cure for the vast majority of patients. The regimen combines two potent antiviral agents with distinct mechanisms of action: sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, and velpatasvir, a pangenotypic inhibitor of the HCV NS5A protein.[3] By targeting two separate and essential components of the viral replication cycle, the combination achieves a powerful synergistic effect and presents a high barrier to the development of viral resistance.

Clinical efficacy is exceptionally high, with pivotal trials demonstrating Sustained Virologic Response (SVR), the established marker for virologic cure, in over 95% of patients across all six major HCV genotypes.[5] Epclusa is indicated for the treatment of adults and pediatric patients aged 3 years and older with chronic HCV genotypes 1, 2, 3, 4, 5, or 6, irrespective of prior treatment experience or the presence of compensated cirrhosis (Child-Pugh A).[7] For the more challenging population of patients with decompensated cirrhosis (Child-Pugh B or C), it is indicated for use in combination with ribavirin.[9]

The safety profile of sofosbuvir/velpatasvir is generally favorable, with headache and fatigue being the most frequently reported adverse reactions.[7] However, its use is accompanied by critical safety considerations. The U.S. Food and Drug Administration (FDA) has issued a