• LITVINOVA ELENA V. Department of Management and Economics of Enterprise, National University of Pharmacy, Kharkov, Ukraine
  • POSILKINA OLGA V. Department of Management and Economics of Enterprise, National University of Pharmacy, Kharkov, Ukraine
  • MASLOVA NATALIIA F. State Enterprise “State Scientific Center of Drugs”, Kharkov, Ukraine


The purpose of the study was to analyze and systematize the literature data on the benefit/risk ratio of sofosbuvir administration in the treatment of patients with chronic hepatitis C and the main trends in its patent protection. Studies were conducted using databases on the Internet: Ukrainian patent office, the European patent office, the US patent office, the Food and drug administration, European Medicines Agency (EMEA), State enterprise “The State Expert Center” of the Ministry of Health of Ukraine. It has used retrospective, logical, systematic and analytical methods. Data from clinical studies abroad and meta-analyses indicate that sofosbuvir is one of the most promising drugs for the treatment of chronic HCV infection. Its indisputable advantages are that this drug can be used with different genotypes of the virus, decompensated liver function, it is well tolerated. Sofosbuvir has an improved safety profile and a low probability of viral resistance. The high cost of sofosbuvir is due to the powerful patent protection. As mechanisms for working with patent barriers, it is recommended to use the flexible mechanisms of the TRIPS Agreement: the grant of compulsory licenses, the implementation of parallel imports, the tightening of the criteria for patentability (prohibition of patenting new forms that do not improve therapeutic efficacy).

Keywords: Sofosbuvir, Patent, Chronic hepatitis C, TRIPS


1. Lanini S, Easterbrook PJ, Zumla A, Ippolito G. Hepatitis c: global epidemiology and strategies for control. Clin Microbiol Infect 2016;22:833-8.
2. Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G. Hepatitis c virus in the new era: perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol 2014;20:9633-52.
3. Axley P, Ahmed Z, Ravi S, Singal AK. Hepatitis C virus and hepatocellular carcinoma: a narrative review. J Clin Transl Hepatol 2018;6:79-84.
4. Mohamed AA, Elbedewy TA, El-Serafy M, El-Toukhy N, Ahmed W, Ali El Din Z. Hepatitis c virus: a global view. World J Hepatol 2015;7:2676-80.
5. Dultz G, Zeuzem S. Hepatitis c virus: a European perspective. Gastroenterol Clin North Am 2015;44:807-24.
6. Millman AJ, Nelson NP, Vellozzi C. Hepatitis c: review of the epidemiology, clinical care, and continued challenges in the direct acting antiviral era. Curr Epidemiol Rep 2017;4:174-85.
7. Shelepko S. Introduction of innovative methods of treatment of viral hepatitis C into clinical practice: what are the chances of a cure for infection in Ukrainian patients? Weekly Pharm 2017;1106:4-6.
8. Zaller N, Mazhnaya A, Larney S, Islam Z, Shost A, Prokhorova T, et al. Geographic variability in HIV and injection drug use in Ukraine: implications for integration and expansion of drug treatment and HIV care. Int J Drug Policy 2015;26:37-42.
9. Polamreddy P, Vishwakarma V, Gundla R. A review on anti-HCV agents targeting active site and allosteric sites of nonstructural protein 5B [NS5B]. Int J Pharm Pharm Sci 2016;8:1-18.
10. Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez Montero JV, Poveda E, et al. Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother 2013;14:1161-70.
11. Asselah T, Marcellin P, Schinazi RF. Treatment of hepatitis C virus infection with direct-acting antiviral agents: 100% cure? Liver Int 2018;38:7-13.
12. Powdrill MH, Bernatchez JA, Gotte M. Inhibitors of the hepatitis C virus RNA-dependent RNA polymerase NS5B. Viruses 2010;2:2169-95.
13. Ayman G, Yasmine FI, Nabil ME, Mohammad AI. Direct acting anti-hepatitis C virus drugs: clinical pharmacology and future direction. J Transl Int Med 2017;5:8-17.
14. Gupta V, Kumar A, Sharma P, Arora A. Newer direct-acting antivirals for hepatitis C virus infection: perspectives for India. Indian J Med Res 2017;146:23-33.
15. Jhaveri M, Procaccini N, Kowdley KV. Update on hepatitis C treatment: a systematic review of clinical trials. Minerva Gastroenterol Dietol 2017;63:62-73.
16. McConachie SM, Wilhelm SM, Kale-Pradhan PB. New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Expert Rev Clin Pharmacol 2016;9:287-302.
17. Gentile I, Scotto R, Zappulo E, Buonomo AR, Pinchera B, Borgia G. Investigational direct-acting antivirals in hepatitis C treatment: the latest drugs in clinical development. Expert Opin Investig Drugs 2016;25:557-72.
18. Cornberg M, Razavi HA, Alberti A, Bernasconi E, Buti M, Cooper C, et al. A systematic review of hepatitis C virusepidemiology in Europe, Canada and Israel. Liver Int 2011;31:30-60.
19. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virusinto 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 2014;59:318-27.
20. Messina JP, Humphreys, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015;61:77-87.
21. Takeda K, Noguchi R, Namisaki T, Moriya K, Akahane T, Kitade M, et al. Efficacy and tolerability of interferon-free regimen for patients with genotype-1 HCV infection. Exp Ther Med 2018;16:2743-50.
22. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis c virus infection. Geneva: World Health Organization; 2018.
23. EASL (European association for the study of the liver) recommendations on treatment of hepatitis c 2018. J Hepatol 2018;69:461-511.
24. Lynch SM, Wu GY. Hepatitis c virus: a review of treatment guidelines, cost-effectiveness, and access to therapy. J Clin Transl Hepatol 2016;4:310-9.
25. Kayali Z, Schmidt WN. Finally sofosbuvir: an oral anti-HCV drug with wide performance capability. Pharmgenomics Pers Med 2014;7:387-98.
26. Herbst DA, Reddy KR. Sofosbuvir, a nucleotide polymerase inhibitor, for the treatment of chronic hepatitis c virus infection. Expert Opin Investig Drugs 2013;22:527-36.
27. Gentile I, Borgia F, Buonomo AR, Castaldo G, Borgia G. A novel promising therapeutic option against hepatitis c virus: an oral nucleotide NS5B polymerase inhibitor sofosbuvir. Curr Med Chem 2013;20:3733-42.
28. Stedman C. Sofosbuvir, a NS5B polymerase inhibitor in the treatment of hepatitis c: a review of its clinical potential. Ther Adv Gastroenterol 2014;7:131-40.
29. Lawitz E, Mangia A, Wyles D, Rodriguez Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis c infection. N Engl J Med 2013;368:1878-87.
30. Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis 2013;13:401-8.
31. Gane E, Stedman C, Hyland R, Ding X, Svarovskaia E, Symonds W, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med 2018;368:34-44.
32. Kowdley KV, Lawitz E, Crespo I, Hassanein T, Davis MN, DeMicco M, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis c genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet 2013;381:2100-7.
33. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez Torres M, Younossi ZM, Corregidor A, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis c virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 2014;384:1756-65.
34. Jacobson I, Gordon S, Kowdley K, Yoshida E, Rodriguez Torres M, Sulkowski M, et al. Sofosbuvir for hepatitis c genotype 2 or 3 in patients without treatment options. N Engl J Med 2013;368:1867-77.
35. Lawitz EJ, Rodriguez Torres M, Denning J, Mathias A, Mo H, Gao B, et al. All-oral therapy with nucleotide inhibitors sofosbuvir and GS-0938 for 14 d in treatment-naive genotype 1 hepatitis C (nuclear). J Viral Hepat 2013;20:699-707.
36. Harmeet KB, Harmanjit S, Nipunjot G, Navreet KN. Sofosbuvir: a novel treatment option for chronic hepatitis c infection. J Pharmacol Pharmacother 2014;54:278-84.
37. Madhavi S, Prameela R. Bioanalytical method development and validation for the determination of sofosbuvir from human plasma. Int J Pharm Pharm Sci 2017;9:35-41.
38. Caldeira D, Rodrigues FB, Duarte MM, Sterrantino C, Barra M, Gonçalves N, et al. Cardiac harms of sofosbuvir: systematic review and meta-analysis. Drug Saf 2018;41:77-86.
39. Ahmed H, Abushouk AI, Attia A, Gadelkarim M, Gabr M, Negida A, et al. Safety and efficacy of sofosbuvir plus velpatasvir with or without ribavirin for chronic hepatitis c virus infection: a systematic review and meta-analysis. J Infect Public Health 2018;11:156-64.
40. Liu J, Ma B, Cao W, Li M, Bramer WM, Peppelenbosch MP, et al. Direct-acting antiviral agents for liver transplant recipients with recurrent genotype 1 hepatitis c virus infection: systematic review and meta-analysis. Transpl Infect Dis 2019;e13047.
41. Wei B, Ji F, Yeo YH, Ogawa E, Stave CD, Dang S, et al. Systematic review and meta-analysis: real-world effectiveness of direct-acting antiviral therapies in chronic hepatitis C genotype 3 in Asia. Br Med J Open Gastroenterol 2018;5:e000209.
42. Li G, Zang K, Zhang G, Zhu D, Deng X. Efficacy and safety of sofosbuvir-containing regimens in patients co-infected with chronic hepatitis C virus and human immunodeficiency virus: a meta-analysis. Virol J 2018;15:19.
43. Ji F, Wei B, Yeo YH, Ogawa E, Zou B, Stave CD, et al. Systematic review with meta-analysis: effectiveness and tolerability of interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype 1 in routine clinical practice in Asia. Aliment Pharmacol Ther 2018;47:550-62.
44. Morisco F, Granata R, Camera S, Ippolito A, Milella M, Conti F, et al. Optimization of direct anti-viral agent treatment schedule: focus on HCV genotype 3. United European Gastroenterol J 2018;6:225-37.
45. Ahmed H, Elgebaly A, Abushouk AI, Hammad AM, Attia A, Negida A. Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta-analysis. Antivir Ther. 2017;22:369-79.
46. Liao H, Tan P, Zhu Z, Yan X, Huang J. Sofosbuvir in combination with daclatasvir in liver transplant recipients with HCV infection: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2017;41:262-71.
47. Rezaee Zavareh MS, Hesamizadeh K, Behnava B, Alavian SM, Gholami-Fesharaki M, Sharafi H. Combination of ledipasvir and sofosbuvir for the treatment of hepatitis c virus genotype 1 infection: systematic review and meta-analysis. Ann Hepatol 2017;16:188-97.
48. Tao T, Jiang X, Chen Y, Song Y. Efficacy and safety of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis c virus genotype 1 infection: a meta-analysis. Int J Infect Dis 2017;55:56-71.
49. Liao HT, Tan P, Huang JW, Yuan KF. Ledipasvir+sofosbuvir for liver transplant recipients with recurrent hepatitis c: a systematic review and meta-analysis. Transplant Proc 2017;49:1855-63.
50. He QF, Zhang QF, Zhang DZ. Efficacy and safety of ribavirin with sofosbuvir plus ledipasvir in patients with genotype 1 hepatitis C: a meta-analysis. Dig Dis Sci 2016;61:3108-17.
51. Nguyen NH, Yee BE, Chang C, Jin M, Lutchman G, Lim JK, et al. Tolerability and effectiveness of sofosbuvir and simeprevir in the post-transplant setting: systematic review and meta-analysis. Br Med J Open Gastroenterol 2016;3:e000066.
52. Berden FA, Aaldering BR, Groenewoud H, IntHout J, Kievit W, Drenth JP. Identification of the best direct-acting antiviral regimen for patients with hepatitis c virus genotype 3 infection: a systematic review and network meta-analysis. Clin Gastroenterol Hepatol 2017;15:349-59.
53. Fan H, Huang P, Tian T, Wu J, Xia X, Feng Y, et al. Efficacy and safety of sofosbuvir-containing regimens in chronic hepatitis c patients with genotype 2 and 3:a comprehensive analysis of 18 randomized controlled trials. J Gastrointestin Liver Dis 2018;27:159-68.
54. Tong MJ, Chang PW, Huynh TT, Rosinski AA, Tong LT. Adverse events associated with ribavirin in sofosbuvir-based therapies for patients with chronic hepatitis c: a community practice experience. J Dig Dis 2016;17:113-21.
55. Elbaz T, Elserafy M, Elakel W, Mohey MA, Abdo M, Hassany M, et al. Serious adverse events with sofosbuvir combined with interferon and ribavirin: real-life egyptian experience. J Interferon Cytokine Res 2017;37:348-53.
56. Steinbrook R, Redberg RF. The high price of the new hepatitis c virus drugs. JAMA Intern Med 2014;174:1172.
57. Dhingra A, Kapoor S, Alqahtani SA. Recent advances in the treatment of hepatitis c. Discov Med 2014;18:203-8.
58. van de Ven N, Fortunak J, Simmons B, Ford N, Cooke GS, Khoo S, et al. Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis c virus. Hepatology 2015;61:1174-82.
59. Chhatwal J, Kanwal F, Roberts MS, Dunn MA. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med 2015;162:397-406.
60. Najafzadeh M, Andersson K, Shrank WH, Krumme AA, Matlin OS, Brennan T, et al. Cost-effectiveness of novel regimens for the treatment of hepatitis c virus. Ann Intern Med 2015;162:407-19.
61. Trooskin SB, Reynolds H, Kostman JR. Access to costly new hepatitis c drugs: medicine, money, and advocacy. Clin Infect Dis 2015;61:1825-30.
62. Iyengar S, Tay Teo K, Vogler S, Beyer P, Wiktor S, de Joncheere K, et al. Prices, costs, and affordability of new medicines for hepatitis c in 30 countries: an economic analysis. PLoS Med 2016;13:e1002032.
63. Luhnen M, Waffenschmidt S, Gerber-Grote A, Hanke G. Health economic evaluations of sofosbuvir for treatment of chronic hepatitis c: a systematic review. Appl Health Econ Health Policy 2016;14:527-43.
64. Access to new medicines in Europe: technical review of policy initiatives and opportunities for collaboration and research. Geneva: World Health Organization; 2015.
65. Umar M, Akhter TS, Akbar I, Nisar G, Osama M, Akhter TS. Role of generics in treatment of hepatitis C infection. J Ayub Med Coll Abbottabad 2016;28:890-4.
66. Heath K. Cost-effectiveness analysis of treatment timing considering the future entry of lower-cost generics for hepatitis C. Clinicoecon Outcomes Res 2018;10:539-50.
67. Stafford N. Sofosbuvir faces fresh patent challenge in Europe. Br Med J 2017;356:j1632.
68. Report of world community advisory board on HCV generics and diagnostics. Forging a path to HCV elimination: simpler tests and affordable generics. Geneva: World Hepatitis Organization; 2017.
69. Zhivitsa DG, Miroshnichenko DV, Kazek VG, Petrovskaya OD, Samoilenko OV. Efficiency of lepidapasive/sopfvbulus in people who inject drugs co-infected with HIV and HCV genotype 1b. Infectious Diseases 2018;3:39-43.
70. Kolesnikova EV. Sophosbuvir in the therapy of chronic viral hepatitis c: facts and hopes. Modern Gastroenterol 2016;4:100-7.
71. Grillon C, Krishtel PR, Mellouk O, Basenko A, Freeman J, Mendão L, et al. Treatment advocate tactics to expand access to antiviral therapy for HIV and viral hepatitis C in low-to high-income settings: making sure no one is left behind. J Int AIDS Soc 2018;21:e25060.
72. Assefa Y, Hill PS, Williams OD. Access to hepatitis c virus treatment: lessons from implementation of strategies for increasing access to antiretroviral treatment. Int J Infect Dis 2018;70:65-8.
73. Douglass CH, Pedrana A, Lazarus JV, 't Hoen EFM, Hammad R, Leite RB, et al. Pathways to ensure universal and affordable access to hepatitis C treatment. BMC Med 2018;16:175.
74. Correa CM. Flexibilities provided by the agreement on trade-related aspects of intellectual property rights. Bull World Health Organ 2018;96:148.
75. 't Hoen EF, Veraldi J, Toebes B, Hogerzeil HV. Medicine procurement and the use of flexibilities in the agreement on trade-related aspects of intellectual property rights, 2001-2016. Bull World Health Organ 2018;96:185-93.
76. 't Hoen EF, Boulet P, Baker BK. Data exclusivity exceptions and compulsory licensing to promote generic medicines in the European Union: a proposal for greater coherence in European pharmaceutical legislation. J Pharm Policy Pract 2017;10:19.
77. Angeli F. With the help of a foreign ally: biopharmaceutical innovation in India after TRIPS. Health Policy Plan 2014;29:280-91.
78. Ramani SV, Urias E. Access to critical medicines: When are compulsory licenses effective in price negotiations? Soc Sci Med 2015;135:75-83.
79. Von Falck A. Compulsory licenses as a defense in pharmaceutical and biotech patent litigation. Pharm Pat Anal 2016;5:351-3.
80. Chaves GC, Oliveira MA, Hasenclever L, de Melo LM. Evolution of the international intellectual property rights system: patent protection for the pharmaceutical industry and access to medicines. Cad Saude Publica 2007;23:257-67.
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How to Cite
V., L. E., V., P. O., & F., M. N. (2019). SOFOSBUVIR: TREATMENT OF CHRONIC HEPATITIS C AND THE MAIN TRENDS IN PATENT PROTECTION. International Journal of Applied Pharmaceutics, 11(4), 8-14.
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