The Clinical Development of Sofosbuvir/Velpatasvir (SOF/VEL, Epclusa®)
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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.
KeywordsDecompensated cirrhosis Elimination Epclusa HCV Pangenotypic SOF/VEL
The authors would like to thank the patients and their families as well as study site staff who participated in the clinical trials of Epclusa.
Compliance with Ethical Standards
Conflict of Interest Diana M. Brainard and John G. McHutchison are employees of Gilead Sciences, Inc.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study. The authors would like to thank the patients and their families as well as study site staff who participated in the clinical trials of Epclusa.
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