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

  • Diana M. BrainardEmail author
  • John G. McHutchison
Part of the Topics in Medicinal Chemistry book series (TMC, volume 32)


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.


Decompensated 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.

Ethical Approval

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

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.


  1. 1.
    Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H (2014) Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 61:S45–S57CrossRefGoogle Scholar
  2. 2.
    Lawitz E, Freilich B, Link J et al (2015) A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1-4 hepatitis C virus. J Viral Hepat 22:1011–1019CrossRefGoogle Scholar
  3. 3.
    Everson GT, Towner WJ, Davis MN et al (2015) Sofosbuvir with velpatasvir in treatment-naïve noncirrhotic patients with genotype 1 to 6 hepatitis C virus infection: a randomized trial. Ann Intern Med 163:818–826CrossRefGoogle Scholar
  4. 4.
    Gane EJ, Hyland RH, An D, McNally J, Brainard DM, Symonds WT, McHutchison JG, Stedman DA (2014) Once daily sofosbuvir with GS-5816 for 8 weeks with or without ribavirin in patients with HCV genotype 3 without cirrhosis result in high rates of SVR12: the ELECTRON2 study. Hepatology 60(4 (suppl)):236AGoogle Scholar
  5. 5.
    Pianko S, Flamm SL, Shiffman ML et al (2015) Sofosbuvir plus velpatasvir combination therapy for treatment-experienced patients with genotype 1 or 3 hepatitis C virus infection: a randomized trial. Ann Intern Med 163:809–817CrossRefGoogle Scholar
  6. 6.
    Feld JJ, Jacobson IM, Hezode C et al (2015) Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 373:2599–2607CrossRefGoogle Scholar
  7. 7.
    Foster GR, Afdhal N, Roberts SK et al (2015) Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 373:2608–2617CrossRefGoogle Scholar
  8. 8.
    Curry MP, O’Leary JG, Bzowej N et al (2015) Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 373:2618–2628CrossRefGoogle Scholar
  9. 9.
    O’Leary J. EASL, 2016, #SAT-169Google Scholar
  10. 10.
    Wyles D, Brau N, Kottilil S et al (2017) Sofosbuvir and velpatasvir for the treatment of hepatitis C virus in patients coinfected with human immunodeficiency virus type 1: an open-label phase 3 study. Clin Infect Dis 65:6–12CrossRefGoogle Scholar
  11. 11.
    Gilead Sciences Inc. (2018) EPCLUSA® (sofosbuvir and velpatasvir) tablets, for oral use. US Prescribing Information, Foster CityGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinical Research, Liver Disease Therapeutic AreaGilead Sciences, Inc.Foster CityUSA
  2. 2.Clinical ResearchGilead Sciences, Inc.Foster CityUSA

Personalised recommendations