Vosevi

Drug Overview

Vosevi ([sofosbuvir + velpatasvir + voxilaprevir]) is Gilead’s third-generation, pan-genotypic, interferon-free regimen. The fixed-dose combination contains the hepatitis C virus nucleotide NS5B inhibitor sofosbuvir, a second-generation NS5A inhibitor (velpatasvir), and the company’s NS3 protease inhibitor (voxilaprevir). The combination is approved in the US and five major EU markets (France, Germany, Italy, Spain, and the UK) as a 12-week salvage regimen for the treatment of direct-acting antiviral (DAA)-experienced genotype (GT)-1/2/3/4/5/6 chronic hepatitis C patients. Within the EU, Vosevi’s label also allows for its use as an eight-week regimen in treatment-naïve non-cirrhotic patients, and as a 12-week regimen in treatment-naïve cirrhotic patients.

Based on its inclusion of three modes of action and its proven efficacy in the POLARIS-1 and POLARIS-4 studies, Vosevi is forecasted to dominate the treatment algorithm for DAA-experienced patients, but its commercial potential will be severely limited by the small size of this subgroup (<5% of patients). Notably, Vosevi maintained high cure rates in patients with pre-existing resistance-associated substitutions, which will allow it to emerge as the preferred agent over AbbVie’s Mavyret ([glecaprevir + pibrentasvir]), which demonstrated uncompetitive efficacy in patients with baseline resistance to both an NS5A inhibitor and an NS3/4A protease inhibitor. Indeed, Mavyret’s EU label specifically recommends against its use in NS5A- or NS3/4A-experienced patients, paving the way for Vosevi to occupy the DAA-experienced niche and to command a higher price tag in exchange for addressing one of the final unmet needs of chronic hepatitis C treatment.