The Clinical Development of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX, Vosevi®)

Abstract

The single-tablet regimen of sofosbuvir (SOF), an HCV nucleotide analog NS5B polymerase inhibitor; velpatasvir (VEL), an HCV NS5A inhibitor; and voxilaprevir (VOX), an NS3/4 protease inhibitor, provides a highly efficacious, safe, and salvage regimen for patients with genotype 1 to 6 HCV infection with and without compensated cirrhosis who were previously unsuccessfully treated with direct-acting antivirals (DAAs). The clinical development program for SOF/VEL/VOX focused on generating safety and efficacy data in DAA-experienced patients without retreatment options as well as assessing the possibility of shortening treatment duration for DAA-naive patients. The Phase 3 studies enrolled and treated over 1,000 genotype 1–6 HCV-infected patients with SOF/VEL/VOX. In DAA-experienced patients treated with 12 weeks of SOF/VEL/VOX, the overall SVR rate was 97%, and high SVR rates were observed across all genotypes irrespective of prior DAA regimen, cirrhosis status, or the presence of baseline resistance-associated substitutions (RASs), supporting its use as a retreatment regimen. In DAA-naive patients treated with 8 weeks of SOF/VEL/VOX, the overall SVR rate was 95% making it an alternative treatment option for regions in which a shorter duration is of particular interest.