Medication of Chronic Hepatitis C: A Review on Sofosbuvir as a New Antiviral Drug

Authors

  • Adel Abdel-Moneim 1Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, 62511, Beni-Suef Egypt.
  • Shimaa Ramadan

Keywords:

Peginterferon, chronic hepatitis C, ribavirin, direct antiviral agents, sofosbuvir.

Abstract

In the last decade, standard of care (SOC) anti-HCV treatment has been represented by the combination of Peginterferon (Peg-IFN) plus ribavirin (Rbv). The main disadvantages of Peg-IFN plus Rbv therapy were suboptimal rates of sustained virological response (SVR) in difficult-to-treat patients and side effects profile resulting in poor tolerability. Therefore, strategies to improve SVR rates and limited side effects have been an important issue for clinical physicians. Recently, direct antiviral agents (DAAs) opened the gate for a new era for management of HCV and have revolutionized the treatment of chronic hepatitis c (CHC) patients. Furthermore, the approval of sofosbuvir by FDA represents the first key step towards the new era in the management of CHC patients, since it is the first approved DAAs with excellent tolerability and favorable pharmacokinetic profile, limited potential for drug interactions, higher specificity, shorter treatment durations, low side effects, oral administration, potent antiviral activity and high genetic barrier against all HCV genotypes and acts as a chain terminator during the HCV replication process. Sofosbuvir efficacy and safety was demonstrated in many large and well-designed phase 2 and phase 3 clinical trials like PROTON, ATOMIC, NEUTRINO, ELECTRON, QUANTUM, FISSION, FUSION, POSITRON and LONSTAR studies. In this concept, sofosbuvir represents an almost ideal backbone, especially in difficult-to-treatCHCpatients with cirrhosis or liver impairment, liver transplant recipients, and co-infection with HIV. This review summarizes the development of different anti-HCV agents, and also provides an overview of sofosbuvir clinical efficacy and discussing key results and potential future developments.

References

[1] Mohd HK, Groeger J, Flaxman AD, Wiersma ST,(2013), Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence, Hepatology, 57,1333–42.
[2] Naggie S, Patel K, McHutchison J, (2010),Hepatitis C virus directly acting antivirals: current developments with NS3/4A HCV serine protease inhibitors, J Antimicrob Chemother. 65, 2063–69.
[3] Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP,(2006), The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide, Hepatology, 45 (4), 529–38.
[4] Kayali Z, Labrecque DR, Schmidt WN, (2006),Treatment of hepatitis C cryoglobulinemia: mission and challenges, Curr Treat Options Gastroenterol, 9,497–507.
[5] Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, et al.,(2015), Global Distribution and Prevalence of Hepatitis C Virus Genotypes, Hepatology, 61, 77-87.
[6] Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ, (2002),The prevalence of hepatitis C virus infection in the United States, 1999 through 2002, Ann Intern Med, 144,705-14.
[7] Razavi H, El-Khoury AC, Elbasha E, Estes C, Pasini K, Poynard T, Kumar R, (2013),Chronic Hepatitis C Virus (HCV) Disease Burden and Cost in the United States, Hepatology, 57(6), 2164–70
[8] Hatzakis A, Wait S, Bruix J, Buti M, Carballo, M, et al, (2011),The state of hepatitis B and C in Europe : report from the hepatitis B and C summit conference, J Viral Hepatol, 18(1), 1-16.
[9] Papatheodoridis, G , Hatzakis, A ,(2012), Public health issues of hepatitis C virus infection, Best Practice &Research Clinical Gastroenterololgy, 26,371-80.
[10] European Association for the Study of the Liver (EASL),(2011), clinical practice guidelines: management of hepatitis C virus infection, J Hepatol, 55,245–64.
[11] Nguyen LH, Ko S, Wong SS, Tran PS, Trinh HN, et al.,(2011), Ethnic differences in viral dominance patterns in patients with hepatitis B virus and C virus dual infection, Hepatology ,53,1839-45.
[12] Lindenbach, BD, Rice, CM, (2005), Unraveling hepatitis C virus replication from genome to function, Nature, 436,933–38.
[13] Shimotohno K1, Tanji Y, Hirowatari Y, Komoda Y, Kato N, Hijikata M,(1995), Processing of the hepatitis C virus precursor protein, J Hepatol , 22(1 Suppl),87-92.
[14] Branch AD, Stumpp DD, Gutiezrre JA,(2005), The hepatitis virus alternate reading frame (ARF) and its Family of navel products: the alternate reading frame protein/ F-protein, the double- frame shift protein, and others, Semin Liv Dis, 25,105-17.
[15] Varaklioti A, Vassilaki, N , Georgopoulou, U ,(2002), Alternate translation occurs within the core coding region of the hepatitis C viral genome, J Biol Chem, 277(20), 17713-21.
[16] Appel N, Schaller T, Penin F, Bartenschlager R,(2006), From structure to function: new insights into hepatitis C virus RNA replication, J Biol Chem, 281,9833–36.
[17] Ma Y, Yates J, Liang Y, Lemon SM, Yi M,(2008), NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly, J Virol, 82,7624–39.
[18] Alexopoulou, A , Karayiannis, P ,(2015), Interferon-based combination treatment for chronic hepatitis C in the era of direct acting antivirals, Ann Gastroenterol , 28(1), 55–65.
[19] Martinot-Peignoux M, Stern C, Maylin S, Ripault MP, Boyer N, et al.,(2010), Twelve weeks post-treatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin, Hepatology, 2010, 51,1122-26.
[20] Gentile I, Borgia F, Buonomo AR, Castaldo G, Borgia G ,(2013), A novel promising therapeutic option against hepatitis C virus: An oral nucleotide NS5B polymerase inhibitor sofosbuvir, Curr Med Chem, 20,3733–42.
[21] Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, et al.,(1986), Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon, A preliminary report, N Engl J Med., 315,1575–78.
[22] Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai, MY, et al.,(2000), Peg-interferon alfa-2a in patients with chronic hepatitis C, N Engl J Med., 343(23),1666-72.
[23] Heathcote EJ, Shiffman ML, Cooksley WG, Dusheiko GM, Lee SS, et al.,(2000), Peg-interferon alfa-2a in patients with chronic hepatitis C and cirrhosis, N Engl J Med, 343(23),1673-80.
[24] Fried, MW,(2002), Side effects of therapy of hepatitis C and their management.Hepatology, 36, S237-44.
[25] Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di-Costanzo GG ,et al.,(2010), Peg-interferon Alfa-2a Plus Ribavirin is More Effective than Peg-interferon Alfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus Infection, Gastroenterology, 138(1),116–22.
[26] Berenguer J, lvarez-Pellicer JA, Mart?´n PM, Opez-Aldeguer IL, Von-Wichmann MA,(2009), Sustained Virological Response to Interferon Plus Ribavirin Reduces Liver-Related Complications and Mortality in Patients Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus, Hepatology, 50(2),407-13. (2):407-4013. HEPATOLOGY
[27] Manns MP, Mc-Hutchison JG, Gordon SC,(2001), Peg-interferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial, Lancet, 358,958–65.
[28] Fried MW, Shiffman ML, Reddy KR,(2002), Peg-interferon alfa-2a plus ribavirin for chronic hepatitis C virus infection, N Engl J Med, 347,975–82.
[29] Hadziyannis SJ, Sette H J, Morgan TR, (2004),Peg-interferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med, 140,346–355.
[30] Hunyady B, Kovács B , Battyáni Z ,(2011), Side-effects of pegylated interferon plus ribavirin therapy with or without protease inhibitor direct acting antiviral agents during treatment of chronic hepatitis C virus infection, Orv Hetil , 152(50),1997-09.
[31] European Association for the Study of the Liver (EASL),(2011), Clinical Practice Guidelines: management of hepatitis C virus infection, J Hepatol , 55,245–264.
[32] Alexopoulou A, Papatheodoridis GV,(2012), Current progress in the treatment of chronic hepatitis C,World J Gastroenterol, 18,6060–69.
[33] Anantharamu A, Sharma S, Sharma AK, Gupta AK, Dahiya N, Brashier DB,(2014), A review of the current anti-HCV therapy: Are we finally ready for interferon-free regimens, I J of Nutr Pharm Neurolog Dise, 4(5), 6-11.
[34] Kayali Z, Schmidt WN ,(2014), Finally sofosbuvir: an oral anti-HCV drug with wide performance capability, Pharmgenomics Pers Med, 7,387–98.
[35] Chatel-Chaix L, Baril M, Lamarre D ,(2010),Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel, Viruses , 2(8), 1752–65.
[36] Vaidya A , Perry CM ,(2013), Simeprevir: first global approval, Drugs, 73 (18) , 2093–06.
[37] Gottwein JM, Scheel TK, Jensen TB, Ghanem L, Bukh J ,(2011), Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses. astroenterology, 141(3),1067-79.
[38] US Food and Drug Administration, Simeprevir prescribing information, Silver Spring, [accessed 2014 May 5], Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/205123s001lbl.pdf
[39] Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, et al.,(2014), 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 randomized study, Lancet, 384, 1756–65,
[40] Asselah T, Marcellin P, (2014), Second-wave IFN-based triple therapy for HCV genotype 1 infection: simeprevir, faldaprevir and sofosbuvir, Liver Int, 34 (1), 60–68.
[41] Sulkowski MS, Bourlie`re M, Bronowicki GP, Asselah T, Pawlotsky GM, et al.,(2013),Faldaprevir combined with pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic genotype 1 HCV, SILEN-C1 trial, Hepatology, 57 (6), 2143–54.
[42] Kanda T, Yokosuka O, Omata M,(2015), Faldaprevir for the Treatment of Hepatitis C, Int J Mol Sci , 16(3),4985-96.
[43] Mc-Phee F, Hernandez D, Yu F, Ueland J, Monikowski A , et al.,(2013), Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and sunaprevir, Hepatology, 58,902–11
[44] Marcellin P, Manns MP, Janczewska E, Muir AJ, Wu X, Trenkle JD, et al. ,(2013), 12 weeks response- guided treatment with the NS5A inhibitor, GS-5885, the NS3 protease inhibitor, GS-9451, plus pegylated interferon and ribavirin in treatment naive genotype 1 hepatitis C infected patients, J Hepatol. 58(2), S355.
[45] Vince B, Hill JM, Lawitz EJ, O’Riordan W, Webster LR, Gruener DM, et al.,(2014), A randomized, double-blind, multiple-dose study of the pan-genotypic NS5A inhibitor samatasvir in patients infected with hepatitis C virus genotype 1, 2, 3 or 4, J Hepatol, 60 (5), 920–27
[46] German P, Mathias A, Pang P, Yang C, Yang C, Han L, et al.,(2013), Healthy volunteer first-in-human evaluation of GS-5816, a novel second generation broad-genotypic NS5A inhibitor with potential for once-daily dosing, In: Abstract presented at the 48th annual meeting of the European association for the study of the liver, Amsterdam (The Netherlands).
[47] Guedj J, Dahari H, Rong L, Sansone ND, Nettles RE, Cotler SJ, et al.,(2013), Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life, Proc Natl Acad Sci USA, 110 (10), 3991–96
[48] Suzuki F, Toyota J, Ikeda K, Chayama K, Mochida S , Hayashi N, et al. ,(2014),A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for HCV genotype 1 infection, Antivir Ther, 19, , 491– 99
[49] Izumi N, Yokosuka O, Kawada N, Osaki Y, Yamamoto K, Sata M, et al.,(2014), Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1, Antivir Ther, 19,501– 10
[50] Wong KA, Worth A, Martin R, Svarovskaia E, Brainard DM, Lawitz E, et al.,(2013), Characterization of hepatitis C virus resistance from a multiple dose clinical trial of the novel NS5A inhibitor GS-5885 Antimicrob Agents Ch, 57 (12),6333–40
[51] Lawitz EJ, Gruener D, Hill JM, Marbury T, Moorehead L, Mathias, A, et al. ,(2012), A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C, J Hepatol, 57 (1), 24–31
[52] Flisiak R, Pawlotsky JM, Crabbe R, Calistru PI, Kryczka W, et al.,(2011), Once-daily alisporivir (DEB025) plus peginterferon alfa-2a/ribavirin results in superior sustained virologic response in chronic hepatitis C genotype 1 treatment-naive patients, J Hepatol, 54(1), S2
[53] Koch, U, Narjes, F,(2007), Recent progress in the development of inhibitors of the hepatitis C virus RNA-dependent RNA polymerase, Curr Top Med Chem, 7(13),1302-29.
[54] Kwong AD, McNair L, Jacobson I, George S ,(2008),Recent progress in the development of selected hepatitis C virus NS3.4A protease and NS5B polymerase inhibitors, Curr Opin Pharmacol , 8,522–31.
[55] Belkacem AA, Guichou JF, Brillet R, Ahnou N, Hernandez E ,et al.,(2014), Inhibition of RNA binding to hepatitis C virus RNA-dependent RNA polymerase: a new mechanism for antiviral intervention, Nucl Acids Res, 42 (14), 9399-09.
[56] Legrand-Abravanel F, Nicot F, Izopet J ,(2010), New NS5B polymerase inhibitors for hepatitis C, Expert Opin Invest Drugs, 19,963-75
[57] Trivella JP1, Gutierrez J, Martin P,(2015), Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C, Expert Opin Pharmacother, 16(4),617-24.
[58] Pawlotsky JM1,(2013), NS5A inhibitors in the treatment of hepatitis C, J Hepatol, 59(2),375-82.
[59] Hassanein T, Lawitz E, Crespo I, Davis M, DeMicco MP, Nelson DR, et al.,(2012), Once daily sofosbuvir (GS-7977) plus PEG/RBV: high early response rates are maintained during post-treatment follow-up in treatment-naive patients with HCV genotype 1, 4, and 6 infections in the ATOMIC study, Hepatology, 56 ,307A
[60] Mathias MA, Cornpropst D, Clemons J, Denning WT,(2012), No clinically significant pharmacokinetic drug–drug interactions between sofosbuvir (GS-7977) and the immunosuppressants, cyclosporine a or tacrolimus in healthy volunteers, Hepatology, 56, 1063A–64A
[61] Ron W,"Gilead’s HCV drug sofosbuvir approved by the FDA but accessible for how many?". Doctors of the World, 2014.
[62] Wodak A , An overview of Hepatitis C; Clinical Management in Opiate Pharmacotherapy Settings Australian Society for HIV Medicine Inc (ASHM), National Viral Hepatitis Education Program, 2009,1-4.
[63] Smith MW, Walters KA, Korth MJ, Fitzgibbon M, Proll S, Thompson JC, et al.,(2006), Gene expression patterns that correlate with hepatitis C and early progression to fibrosis in liver transplant recipients, Gastroenterology, 130,179–87.
[64] Fung A, Jin Z, Dyatkina N, Wang G, Beigelman L, Deval J ,(2014), Efficiency of incorporation and chain termination determines the inhibition potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase, Antimicrobial Agents and Chemotherapy, 58 (7), 3636–45.
[65] Lam AM, Espiritu C, Bansal S, Micolochick-Steuer HM, Niu C, Zennou V, et al.,(2012), Genotype and subtype pro-ling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus, Antimicrob Agents Chemother, 56,3359-68.
[66] Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, et al.,(2010), Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977, J Biol Chem, 285 (45), 34337–47.
[67] Chae HB, Park SM, Youn SJ(2013),, Direct-acting antivirals for the treatment of chronic hepatitis C: open issues and future perspectives, Scientific World Journal, 704912.
[68] Degasperi E, Aghemo A ,(2014),Sofosbuvir for the treatment of chronic hepatitis C: between current evidence and future perspectives, Hepat Med. 6, 25–33.
[69] Cholongitas E, Papatheodoridis GV,(2014), Sofosbuvir: a novel oral agent for chronic hepatitis C, Ann Gastroenterol, 27(4), 331–337.
[70] Jacobson IM, Gordon SC, Kowdley KV, Kowdley KV , Yoshida EM ,et al. ,(2013), Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options, N Engl J Med, 368(20),1867–77.
[71] Kirby B, Gordi T, Symonds WT, Kearney BP ,Mathias A,(2013), Population pharmacokinetics of sofosbuvir and its major metabolite (GS-331007) in healthy and HCV-infected adult subjects; 64th Annual Meeting of the American Association for the Study of Liver Diseases, November 1–5, Washington, DC.
[72] Elbaza T, El-Kassasb M, Esmata G,(2014), New era for management of chronic hepatitis C virus using direct antiviral agents: A review. J Adv Res, doi:10.1016/j.jare.2014.11.004
[73] Lawitz E, Lalezari J, Hassanein T, Kowdley K, Poordad F, Sheikh A, et al., (2013),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 randomized, double-blind, phase 2 trial, Lancet Infect, 13, 401–408
[74] Kowdley K, Lawitz E, Crespo I, Hassanein T, Davis M, DeMicco M, et al. ,(2013),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, 381, 2100–07
[75] Gane E, Stedman C, Hyland R, Pang P, Ding X, Symonds W, et al.,(2013), All-oral sofosbuvir-based 12-week regimens for the treatment of chronic HCV infection: the ELECTRON study, J Hepatol, 58(S1–S24), A14
[76] Lalezari JP, Nelson DR, Hyland RH, Lin M, Rossi SJ, Symonds WT, et al.,(2013), Once daily sofosbuvir plus ribavirin for 12 and 24 weeks in treatment-naïve patients with HCV infection: the QUANTUM study, J Hepatol, 58, S236
[77] Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, et al, Sofosbuvir for previously untreated chronic hepatitis C infection, N Engl J Med. 2013, 368,1878–87.
[78] Zeuzem S, Dusheiko G, Salupere R, Mangia A, Flisiak R, et al.,(2013), Sofosbuvir plus ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial, Hepatology, 58(4), 733A.
[79] Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, et al.,(2014),Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR):an open-label, randomised, phase 2 trial, Lancet, 383,515–23.
[80] Lawitz E, Poordad F, Brainanrd D, Brainard DM, Robert H, et al,(2013), Sofosbuvir in combination with Peg-IFN and ribavirin for 12 weeks provides high SVR rates in HCV-infected genotype 2 or 3 treatment experienced patients with and without compensated cirrhosis: results from the LONESTAR-2 study, Hepatology, 58(Suppl 4),1380A.
[81] Gane EJ, Hyl RH, An D, Pang PS, Symonds WT, et al,(2014), Sofosbuvir/Ledipasvir fixed dose combination is safe and effective in difficult-to-treat populations including genotype-3 patients, decompensated genotype-1 patients, and genotype-1 patients with prior Sofosbuvir treatment experience, J Hepatol, 60:S3-S4.
[82] Fontana R, Hughes E, Bifano M, Appelman H, Dimitrova D, Hindes R, et al.,(2013), Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C, Am J Transplant, 1601–05
[83] Charlton M, Gane E, Manns MP, Brown RSJ, Curry MP, et al.,(2015), Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology, 148(1):108-17.
[84] Rodriguez-Torres M, Lawitz E, Kowdley KV, Nelson DR, Dejesus E, Mc-Hutchison JG, et al,(2013), Sofosbuvir (GS-7977) plus peg-interferon/ribavirin in treatment-naïve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial, J Hepatol. 58,663–68.
[85] Younossi Z, Stepanova M, Mir H, Jacobson I, Gane E, Nader F, et al. ,(2013), Minimal impact of sofosbuvir + ribavirin on health related quality of life (HRQL) compared to pegylated interferon + ribavirin for chronic hepatitis C: results from FISSION + POSITRON trials, J Hepatol, 58(S567–S577), Abstract 1431
[86] US Food and Drug Administration,(2015), FDA Drug Safety Communication.
http://www.fda.gov/Drugs/DrugSafety/ucm439484.htm
[87] Karageorgopoulos DE, El-Sherif O, Bhagani S, Khoo SH,(2014) Drug interactions between antiretrovirals and new or emerging direct-acting antivirals in HIV/hepatitis C virus confection, Curr Opin Infect Dis, 27(1), 36-45.
[88] Levin J (2012), GS-7977 and HIV ARTs PK - No Clinically Significant Pharmacokinetic Interactions between Sofosbuvir (GS-7977) and HIV Antiretro virals Atripla, Rilpivirine, Darunavir/Ritonavir, or Raltegravir in Healthy Volunteers. AASLD- 63rd Annual Meeting of the American Association for the Study of Liver Diseases.

Downloads

Published

2015-05-29

How to Cite

Abdel-Moneim, A., & Ramadan, S. (2015). Medication of Chronic Hepatitis C: A Review on Sofosbuvir as a New Antiviral Drug. American Scientific Research Journal for Engineering, Technology, and Sciences, 13(1), 1–23. Retrieved from https://www.asrjetsjournal.org/index.php/American_Scientific_Journal/article/view/766