Table of Contents
Drug Summary
Sofosbuvir-velpatasvir-voxilaprevir (Figure 1) and (Figure 2) is the first pangenotypic fixed-dose tablet that includes medications from three different HCV antiviral classes. This combination fills an important role as a pangenotypic regimen for persons who have experienced treatment failure with DAA therapy and has emerged as the first-line salvage option for retreatment of HCV infection in these individuals. The presence of NS5A, NS3 or NS5B resistance-associated substitutions pre-treatment did not appear to influence the likelihood of SVR, and 12 weeks of monotherapy without ribavirin produced high SVR rates (96%) in DAA-experienced individuals. Unfortunately, the presence of an HCV protease inhibitor in voxilaprevir does not make this an option for treatment-experienced persons who have moderate or severe liver disease (Child-Turcotte-Pugh B or C cirrhosis).
Adverse Effects
The most common adverse effects, observed in at least 10% of phase 3 trial participants, were headache, fatigue, diarrhea, and nausea.
Class and Mechanism
Sofosbuvir-velpatasvir-voxilaprevir is an oral fixed-dose combination of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor, velpatasvir, an NS5A replication complex inhibitor, and voxilaprevir, an NS3/4A protease inhibitor. Sofosbuvir is a nucleotide prodrug that is metabolized to form the pharmacologically active uridine analog triphosphate (GS-461203), and acts as a chain terminator for the NS5B polymerase. Velpatasvir (formerly GS-5816) has potent in vitro anti-HCV activity across all genotypes at the picomolar level. Voxilaprevir is a reversible inhibitor of the NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV encoded polyprotein, and has been shown to have pangenotypic activity including activity against most resistance-associated substitutions.
Cost and Medication Access
Gilead Sciences has an active sofosbuvir-velpatasvir-voxilaprevir patient assistance program for eligible patients with hepatitis C who do not have insurance and are not covered by Medicaid or Medicare. Information regarding the Gilead Sciences sofosbuvir-velpatasvir-voxilaprevir patient assistance program can be obtained at the Support Path website or by calling 1-855-769-7284.
Key Drug Interactions
For complete information on sofosbuvir-velpatasvir-voxilaprevir-related drug interactions, see the Drug Interactions section in the Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi) Prescribing Information.
Figures
Figure 1. Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi) Bottle
Photo: Andrew Karpenko, University of Washington
Figure 2. Sofosbuvir-Velpatasvir-Voxilaprevir (Vosevi) Pill
Photo: Andrew Karpenko, University of Washington