The Clinical Development of Sofosbuvir/Velpatasvir (SOF/VEL, Epclusa®)

Abstract

The single-tablet regimen of sofosbuvir (SOF), an HCV nucleotide analog NS5B polymerase inhibitor, and velpatasvir (VEL), a second-generation HCV NS5A inhibitor, provides a highly efficacious, safe, and simple treatment regimen for patients with genotype 1–6 HCV infection. The clinical development program for SOF/VEL focused on generating safety and efficacy data across a broad range of patient populations to support a single treatment duration for all patients and therapeutic options for patients with compensated and decompensated liver disease. Three Phase 2 studies defined the optimal dose of VEL as 100 mg for a fixed-dose combination tablet with 400 mg of SOF and demonstrated that the treatment duration of 12 weeks provided high SVR rates across all genotypes irrespective of cirrhosis status, prior treatment history, or the presence of baseline resistance-associated substitutions (RASs). The Phase 3 studies enrolled and treated over 1,000 genotype 1–6 HCV-infected patients with 12 weeks of SOF/VEL. In patients with compensated cirrhosis, the overall SVR rate was 98%, and with SOF/VEL + RBV in patients with decompensated cirrhosis, the SVR rate was 94%. With minimal drug-drug interactions and no need for on-treatment safety monitoring, SOF/VEL for 12 weeks provides an important treatment option for patients of all genotypes and is ideally suited to address the global epidemic of chronic HCV infection.