Skip to main content

Sofosbuvir/Velpatasvir/Voxilaprevir: A Review in Chronic Hepatitis C

Abstract

A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi®) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1–6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients. However, 8 weeks of sofosbuvir/velpatasvir/voxilaprevir was inferior to 12 weeks of sofosbuvir/velpatasvir in cirrhotic or non-cirrhotic DAA-naïve patients with HCV genotype 1, 2, 4, 5 or 6 infection and non-cirrhotic DAA-naïve patients with HCV genotype 3 infection, mostly due to an insufficient treatment period. Sofosbuvir/velpatasvir/voxilaprevir was generally well tolerated, with most adverse events being of mild or moderate intensity. The most common adverse events included headache, fatigue, nausea and diarrhoea. In conclusion, sofosbuvir/velpatasvir/voxilaprevir is an important and effective option for the treatment of HCV genotype 1–6 infection in adults, especially those who have previously failed a DAA therapy with or without an HCV NS5A inhibitor.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Soriano V, Benitez-Gutierrez L, Arias A, et al. Evaluation of sofosbuvir, velpatasvir plus voxilaprevir as fixed-dose co-formulation for treating hepatitis C. Expert Opin Drug Metab Toxicol. 2017;13:1015–1022. https://doi.org/10.1080/17425255.2017.1359254.

    CAS  Article  PubMed  Google Scholar 

  2. Carter W, Connelly S, Struble K. Reinventing HCV treatment: past and future perspectives. J Clin Pharmacol. 2017;57(3):287–96.

    CAS  Article  PubMed  Google Scholar 

  3. Gilead Sciences Inc. US prescribing information: Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir) tablets. 2017. http://www.gilead.com/. Accessed 28 Sept 2017.

  4. European Medicines Agency. Vosevi 400 mg/100 mg/100 mg film-coated tablets: summary of product characteristics. 2017. http://www.ema.europa.eu/ema/. Accessed 28 Sept 2017.

  5. Greig SL. Sofosbuvir/velpatasvir: a review in chronic hepatitis C. Drugs. 2016;76(16):1567–78.

    CAS  Article  PubMed  Google Scholar 

  6. Wyles D, Thompson A, Lawitz E, et al. No impact of RASs on the high efficacy of SOF/VEL/VOX for 8 weeks in DAA-naïve patients: an integrated resistance analysis of the POLARIS-2 and POLARIS-3 studies [abstract no. THU-257 plus poster]. J Hepatol. 2017;66(1 Suppl):S303.

    Article  Google Scholar 

  7. Sarrazin C, Cooper CL, Manns MP, et al. No impact of RASs on the high efficacy of SOF/VEL/VOX for 12 weeks in DAA-experienced patients: an integrated resistance analysis of the POLARIS-1 and POLARIS-4 studies [abstract no. THU-248 plus poster]. J Hepatol. 2017;66(1 Suppl):S299.

    Article  Google Scholar 

  8. Jacobson IM, Lawitz E, Gane EJ, et al. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology. 2017;153(1):113–22.

    CAS  Article  PubMed  Google Scholar 

  9. Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376(22):2134–46.

    Article  PubMed  Google Scholar 

  10. Taylor JG, Appleby T, Barauskas O, et al. Preclinical profile of the pan-genotypic HCV NS3/4A protease inhibitor GS-9857 [abstract no. P0899]. J Hepatol. 2015;62(Suppl 2):S681.

    Article  Google Scholar 

  11. Garrison KL, Kirby B, Stamm LM, et al. Drug–drug interaction profile of sofosbuvir/velpatasvir/voxilaprevir fixed-dose combination [abstract no. FRI-187]. J Hepatol. 2017;66(1 Suppl):S492–3.

    Article  Google Scholar 

  12. Gane EJ, Schwabe C, Hyland RH, et al. Efficacy of the combination of sofosbuvir, velpatasvir, and the NS3/4A protease inhibitor GS-9857 in treatment-naive or previously treated patients with hepatitis C virus genotype 1 or 3 infections. Gastroenterology. 2016;151(3):448–56.

    CAS  Article  PubMed  Google Scholar 

  13. Lawitz E, Reau N, Hinestrosa F, et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with genotype 1 hepatitis C virus infection in an open-label, phase 2 trial. Gastroenterology. 2016;151(5):893–901.

    CAS  Article  PubMed  Google Scholar 

  14. Gane EJ, Kowdley KV, Pound D, et al. Efficacy of sofosbuvir, velpatasvir, and GS-9857 in patients with hepatitis C virus genotype 2, 3, 4, or 6 infections in an open-label, phase 2 trial. Gastroenterology. 2016;151(5):902–9.

    CAS  Article  PubMed  Google Scholar 

  15. Lawitz E, Poordad F, Wells J, et al. Sofosbuvir–velpatasvir–voxilaprevir with or without ribavirin in direct-acting antiviral-experienced patients with genotype 1 hepatitis C virus. Hepatology. 2017;65(6):1803–9.

    CAS  Article  PubMed  Google Scholar 

  16. Younossi ZM, Stepanova M, Jacobson I, et al. High efficacy is accompanied with substantial gains in patient reported outcomes in cirrhotic patients with chronic hepatitis C treated with sofosbuvir (SOF), velpatasvir with or without voxilaprevir (VOX): data from POLARIS 1, 2, 3 and 4 [abstract no. LBP-544]. J Hepatol. 2017;66(1 Suppl):S114.

    Article  Google Scholar 

  17. Younossi ZM, Stepanova M, Jacobson IM, et al. Sofosbuvir/velpatasvir (SOF/VEL) with or without voxilaprevir (VOX) is associated with excellent efficacy and significant improvements of patient-reported outcomes (PROS) during treatment and after achieving sustained virologic response (SVR) [abstract no. 508]. Gastroenterology. 2017;152(5 Suppl 1):S1062.

    Article  Google Scholar 

  18. Grebely J, Jacobson IM, Kayali Z, et al. SOF/VEL/VOX for 8 or 12 weeks is well tolerated and results in high SVR12 rates in patients receiving opioid substitution therapy [abstract no. FRI-235]. J Hepatol. 2017;66(1 Suppl):S513–4.

    Google Scholar 

  19. Roberts SK, Cooper CL, Lawitz E, et al. SOF/VEL/VOX results in high SVR12 rates when administered for 12 weeks in DAA-experienced patients or for 8 Weeks in DAA-naïve patients: an integrated analysis of the POLARIS-1, POLARIS-2, POLARIS-3 and POLARIS-4 studies [abstract no. SAT-280 plus poster]. J Hepatol. 2017;66(1 Suppl):S741.

    Article  Google Scholar 

  20. European Medicines Agency. Vosevi: EPAR-public assessment report 2017. http://www.ema.europa.eu/ema/. Accessed 28 Sept 2017.

  21. Younossi ZM, Stepanova M, Gordon S, et al. Patient-reported outcomes following treatment of chronic hepatitis C virus infection with sofosbuvir and velpatasvir, with or without voxilaprevir. Clin Gastroenterol Hepatol. 2017. https://doi.org/10.1016/j.cgh.2017.11.023.

    Google Scholar 

  22. Manns M, Gane EJ, Willems BE, et al. The safety and tolerability of SOF/VEL/VOX for 8 or 12 weeks in > 1,000 patients treated in the POLARIS-1, POLARIS-2, POLARIS-3, and POLARIS-4 studies: an integrated analysis [abstract no. SAT-236 plus poster]. J Hepatol. 2017;66(1 Suppl):S722–3.

    Article  Google Scholar 

  23. European Association for the Study of the Liver. EASL recommendations of treatment of hepatitis C 2016. J Hepatol. 2017;66(1):153–94.

    Article  Google Scholar 

  24. European Medicines Agency. Epclusa 400/100 mg film-coated tablets: EU summary of product characteristics. 2016. http://www.ema.europa.eu. Accessed 28 Sept 2017.

  25. The American Association for the Study of Liver Diseases. HCV guidance: recommendations for testing, managing, and treating hepatitis C 2017. https://www.hcvguidelines.org/. Accessed 21 Sept 2017.

  26. National Institute for Health and Care Excellence. Technology appraisal guidance: sofosbuvir–velpatasvir–voxilaprevir for treating chronic hepatitis C. 2018. https://www.nice.org.uk. Accessed 26 Feb 2018.

  27. European Medicines Agency. Maviret 100/40 mg film-coated tablets: EU summary of product characteristics. 2017. http://www.ema.europa.eu. Accessed 07 Feb 2017.

  28. Craxi L, Sacchini D, Refolo P, et al. Prioritization of high-cost new drugs for HCV: making sustainability ethical. Eur Rev Med Pharmacol Sci. 2016;20(6):1044–51.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

During the peer review process, the manufacturer of sofosbuvir/velpatasvir/voxilaprevir was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Young-A Heo.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Young-A Heo and Emma Deeks are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.


Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/A9FCF0601B400E10.

Additional information

The manuscript was reviewed by: L. Benítez-Gutiérrez, Internal Medicine Department & Liver Transplant Uni, Puerta de Hierro Majadahonda Hospital & Research Institute, Madrid, Spain; G. Bertino, Hepatology Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; J. I. Herrero, Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Heo, YA., Deeks, E.D. Sofosbuvir/Velpatasvir/Voxilaprevir: A Review in Chronic Hepatitis C. Drugs 78, 577–587 (2018). https://doi.org/10.1007/s40265-018-0895-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-0895-5