Beyond sofosbuvir: What opportunity exists for a better nucleoside/nucleotide to treat hepatitis C?

Antiviral Research

Volumn 107, Issue 1, 2014, Pages 119-124

  Sofia, Michael J ^a,b  

^a OnCore Biopharma Inc   (United States)

^b Baruch S Blumberg Institute   (United States)

Author keywords

GS 7977; HCV nucleotide polymerase inhibitors; Hepatitis C; Prodrug; Sofosbuvir; Sovaldi

Indexed keywords

2' DEOXY 2' FLUORO 2' METHYLCYTIDINE; ACH 3422; ALS 2158; ALS 220; BALAPIRAVIR; BOCEPREVIR; DSB GS 938; GS 6620; GS 938; IDX 184; IDX 20963; IDX 21437; INX 189; LEDIPASVIR; MERICITABINE; MULTIDRUG RESISTANCE PROTEIN; NUCLEOSIDE; NUCLEOTIDE; NUCLEOTIDE DERIVATIVE; PEGINTERFERON; PSI 352938; RG 7348; RIBAVIRIN; SOFOSBUVIR; TELAPREVIR; UNCLASSIFIED DRUG; URIDINE; VALOPICITABINE; VX 135; 2-((5-(2,4-DIOXO-3,4-DIHYDRO-2H-PYRIMIDIN-1-YL)-4-FLUORO-3-HYDROXY-4-METHYLTETRAHYDROFURAN-2-YLMETHOXY)PHENOXYPHOSPHORYLAMINO)PROPIONIC ACID ISOPROPYL ESTER; ANTIVIRUS AGENT; BENZIMIDAZOLE DERIVATIVE; FLUORENE DERIVATIVE; URIDINE PHOSPHATE;

ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; PRIORITY JOURNAL; REVIEW; TREATMENT DURATION; VIRUS INHIBITION; VIRUS REPLICATION; VIRUS RESISTANCE; ANALOGS AND DERIVATIVES; DRUG APPROVAL; DRUG DEVELOPMENT; HEPATITIS C, CHRONIC; TRENDS;

ANTIVIRAL AGENTS; BENZIMIDAZOLES; DRUG APPROVAL; DRUG DISCOVERY; FLUORENES; HEPATITIS C, CHRONIC; HUMANS; NUCLEOSIDES; NUCLEOTIDES; URIDINE MONOPHOSPHATE;

EID: 84901295105     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2014.04.008     Document Type: Note

References (52)

1. N. Afdhal, K.R. Reddy, D.R. Nelson, E. Lawitz, S.C. Gordon, E. Schiff, R. Nahass, R. Ghalib, R. Herring, J. Lalezari, Z.H. Younes, P.J. Pockros, A.M. Di Bisceglie, S. Arora, G.M. Subramanian, Y. Zhu, H. Dvory-Sobol, J.C. Yang, P.S. Pang, W.T. Symonds, J.G. McHutchison, A.J. Muir, M. Sulkowski, and P. Kwo Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection N. Engl. J. Med. 37 2014 1483 1493
2. N. Afdhal, S. Zeuzem, P. Kwo, M. Chojkier, N. Gitlin, M. Pouti, M. Romero-Gomez, J.P. Zarski, K. Agarwal, P. Buggisch, G.R. Foster, N. Brau, H. Buti, I.M. Jacobson, G.M. Subramanian, X. Ding, H. Mo, J.C. Yang, P.S. Pang, W.T. Symonds, J.G. McHutchison, A.J. Muir, A. Mangia, and P. Marcellin Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection N. Engl. J. Med. 2014 10.1056/NEJMoa1402454
3. Alios, 2014. From < http://www.aliosbiopharma.com >.
4. J.J. Arnold, S.D. Sharma, J. Feng, A. Ray, E.D. Smidansky, M.L. Kireeva, A. Cho, J. Perry, J.E. Vela, Y. Park, Y.K. Xu, Y. Tian, D. Babusis, O. Barauskus, B.R. Peterson, A. Gnatt, M. Kashlev, W. Zhong, and C.E. Cameron Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription of antiviral ribonucleosides PLoS Pathog. 8 11 2012 Retrieved from doi:10,1371/journal.ppat.1003030
5. D. Babusis, M.P. Curry, J. Denning, Y. Park, E. Murakami, N. Afdhal, W. Symonds, J.G. McHutchinson, and A. Ray Nucleotide analog levels in liver explants form HCV infected subjects undergoing liver transplantation after up to 24 weeks sofosbuvir (GS-7977) with ribavirin treatment Hepatology 58 Suppl. 2013 737A
6. E. Callaway Hepatitis C drugs not reaching poor Nature 508 2014 295 296
7. Charlton, M.; Gane, E.; Manns, M.P.; Brown, R.S.; Curry, M.P.; Kwo, P.; Fontana, R.J.; Gilroy, R.; Teperman, L.; Muir, A.; McHutchinson, J.G.; Symonds, W.; Denning, J.; McNair, L.; Arterburn, S.; Terrault, N.; Samuel, D.; Forns, X.; 2013. Sofosbuvir and ribavirin for the treatment of established recurrent hepatitis C infection after liver transplantation: preliminary results of a prospective, multicenter study. In: Paper presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC.
8. Curry, M.P.; Forns, X.; Chung, R.T.; Terrault, N.; Brown, R.S.; Fenkel, J.M.; Gordon, F.; O'Leary, J.; Kuo, A.; Schiano, T.; Everson, G.; Schiff, E.; Befeler, A.; McHutchinson, J.G.; Symonds, W.; Denning, J.; McNair, L.; Arterburn, S.; Moonka, D.; Gane, E.; Afdhal, N.; 2013. Pretransplant sofosbuvir and ribavirin to prevent recurrence of HCV infection after liver transplantation. In: Paper presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC.
9. R.J. Fontana, E.A. Hughes, M. Bifano, H. Appelman, D. Dimitrova, R. Hindes, and W.T. Symonds Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C Am. J. Transplant. 13 2013 1601 1605
10. E.J. Gane, C.A. Stedman, R.H. Hyland, X. Ding, E. Svarovskaia, G.M. Subramanian, W.T. Symonds, J.G. McHutchison, and P.S. Pang Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection Gastroenterology 146 736-743 2014 e731
11. Gilead Sciences, 2013. From Sovaldi(™) [package insert].
12. J. Guedj, P.S. Pang, J. Denning, M. Rodriguez-Torres, E. Lawitz, W. Symonds, and A.S. Perelson Analysis of the hepatitis C viral kinetics during administration of two nucleotide analogues: sofosbuvir (GS-7977) and GS-0938 Antivir. Ther. 2014 (10.3851/IMP2733)
13. Hebner, C.M.; Lee, Y.-J.; Han, B.; Chiu, S.; Yian, Y.; Pagratis, N.; Miller, M.D.; Mo, H.; 2012. In vitro pangenotypic and combination activity of sofosbuvir in stable replicon cell lines. In: Paper presented at the 63rd Meeting of the American Association for the Study of Liver Diseases, Boston, MA. Abs #1875.
14. Herper, M.; 2014. Gilead's hepatitis C drug takes off like a rocket. Retrieved February 21, from < http://www.forbes.com/sites/matthewherper/2014/ 02/21/gileads-hepatitis-c-pill-takes-off-like-a-rocket/ >.
15. J.J. Hoofnagle, and A.H. Sherker Therapy for hepatitis C - the costs of success N. Engl. J. Med. 370 2014 1552 1553
16. Idenix, 2014. From < http://www.idenix.com >.
17. Jacobson, I.; Pockros, P.J.; Lalezari, J.; Lawitz, E.; Rodriguez-Torres, M.; DeJesus, E.; Haas, F.; Martorell, C.; Pruitt, R.; Durham, K.; Srinivasan, S.; Rosario, M.; Jagannatha, S.; Hammond, J.L.; 2009. Antiviral activity of filibuvir in combination with pegylated interferon alfa-2a and ribavirin for 28 days in treatment-naive patients chronically infected with HCV genotype 1. In: Paper presented at the 44th Meeting of the European Association for the Study of Liver Diseases, Copenhagen, Denmark.
18. I.M. Jacobson, S.C. Gordon, K.V. Kowdley, E.M. Yoshida, M. Rodriguez-Torres, M.S. Sulkowski, M.L. Shiffman, E. Lawitz, G. Everson, M. Bennett, E. Schiff, M.T. Al-Assi, G.M. Subramanian, D. An, M. Lin, J. McNally, D. Brainard, W.T. Symonds, J.G. McHutchison, K. Patel, J. Feld, S. Pianko, and D.R. Nelson Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options N. Engl. J. Med. 368 2013 1867 1877
19. D.E. Karageorgopoulos, O. El-Sherif, S. Bhagani, and S.H. Khoo Drug interactions between antivirals and new or emerging direct-acting antivirals in HIV/hepatitis D virus coinfection Curr. Opin. Infect. Dis. 27 2014 36 45
20. R.S. Koff Review article: the efficacy and safety of sofosbuvir, a novel, oral nucleotide NS5B polymerase inhibitor, in the treatment of chronic hepatitis C virus infection Aliment. Pharmacol. Ther. 39 2014 478 487
21. Kohli, A.; Sims, Z.; Marti, M.; Nelson, A.; Osinusi, A.; Bon, D.; Hermann, E.; Kotb, C.; Silk, R.; Teferi, G.; Symonds, W.; Pang, P.S.; McHutchinson, J.G.; Subramanian, G.M.; Polis, M.; Masur, H.; Kottilil, S.; 2014. Combination oral, hepatitis C antiviral therapy for 6 or 12 weeks: results of the synergy trial. In: Paper presented at the 21st Conference on Retroviruses and Opportunistic Infections, Boston, MA.
22. K.B. Kowdley, S.C. Gordon, K.R. Reddy, L. Rossaro, D.E. Bernstein, E. Lawitz, M.L. Shiffman, R. Ghalib, M. Ryan, V. Rustig, M. Chojkier, R. Herring, A.M. Di Bisceglie, P.J. Pockros, G.M. Subramanian, D. An, E. Svarovskaia, R.H. Hyland, P.S. Pang, W.T. Symonds, J.G. McHutchison, A.J. Muir, D. Pound, and M.W. Fried Ledipasvir and sofosbuvir for 8 or 12 weeks of chronic HCV without cirrhosis N. Engl. J. Med. 2014 (10:1056/NEJMoa1402355)
23. Lalezari, J.; Asmuth, D.; Casiro, A.; Vargas, H.; Dubuc Patrick, G.; Liu, W.; Pietropaolo, K.; Zhou, X.J.; Sullivan-Bolyai, J.; Mayers, D.; 2009. Antiviral activity, safety, and pharmacokinetics of IDX184, a liver-targeted nucleotide HCV polymerase inhibitor, in patients with chronic hepatitis C. In: Paper presented at the 60th Annual Meeting of the American Association for the Study of Liver Diseases, Boston, MA.
24. A.M. Lam, C. Espiritu, S. Bansal, H. Micolochick Steuer, V. Zennou, M.J. Otto, and P.A. Furman Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA J. Virol. 85 2011 12334 12342
25. A.M. Lam, C. Espiritu, S. Bansal, H.M. Micolochick Steuer, C. Niu, V. Zennou, M. Keilman, Y. Zhu, S. Lan, M.J. Otto, and P.A. Furman Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus Antimicrob. Agents Chemother. 56 2012 3359 3368
26. Lam, A.M.; Espiritu, C.; Micolochick Steuer, H.; Murakami, E.; Niu, C.; Keilman, M.; Frick, D.N.; Heck, J.A.; Sofia, M.J.; Dhanapalan, N.; Chang, W.; Reddy, P.G.; Ross, B.S.; Chun, B.-K.; Wang, P.; Zhang, H.-R.; Rachakonda, S.; Bao, D.; Otto, M.J.; Furman, P.A.; 2010a. Novel 2′-F-2′-C- methylpurine nucleotide analogs are active inhibitors of HCV replication and lack cross-resistance with other nucleos(t)ide analogs. In: Paper presented at the 60th Annual Meeting of the American Association for the Study of Liver Disease, Boston, MA.
27. A.M. Lam, E. Murakami, C. Espiritu, H.M. Steuer, C. Niu, M. Keilman, H. Bao, V. Zennou, N. Bourne, J.G. Julander, J.D. Morrey, D.F. Smee, D.N. Frick, J.A. Heck, P. Wang, D. Nagarathnam, B.S. Ross, M.J. Sofia, M.J. Otto, and P.A. Furman PSI-7851, a pronucleotide of beta-d-2′-deoxy-2′-fluoro- 2′-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication Antimicrob. Agents Chemother. 54 2010 3187 3196
28. E. Lawitz, A. Mangia, D. Wyles, M. Rodriguez-Torres, T. Hassanein, S.C. Gordon, M. Schultz, M.N. Davis, Z. Kayali, K.R. Reddy, I.M. Jacobson, K.V. Kowdley, L. Nyberg, G.M. Subramanian, R.H. Hyland, S. Arterburn, D. Jiang, J. McNally, D. Brainard, W.T. Symonds, J.G. McHutchison, A.M. Sheikh, Z. Younossi, and E.J. Gane Sofosbuvir for previously untreated chronic hepatitis C infection N. Engl. J. Med. 368 2013 1878 1887
29. E. Lawitz, F.F. Poordad, P.S. Pang, R.H. Hyland, X. Ding, H. Mo, W.T. Symonds, J.G. McHutchison, and F.E. Membreno 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 2014 515 523
30. V. Martel-Laferriere, and D.T. Dieterich GS-7977: a promising nucleotide analog NS5B polymerase inhibitor of HCV Future Virol. 7 2012 537 546
31. Mathias, A.; Cornpropst, M.T.; Clemons, D.; Denning, J.; Symonds, W.; 2012. No clinically significant pharmacokinetic drug-drug interactions between Sofosbuvir (GS-7977) and the immunosuppressants cyclosporine A or tacrolimus in healthy volunteers. In: Paper presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases, Boston, MA.
32. C. McGuigan, K. Madela, M. Aljarah, A. Gilles, A. Brancale, N. Zonta, S. Chamberlain, J. Vernachio, J. Hutchins, A. Hall, B. Ames, E. Gorovits, B. Ganguly, A. Kolykhalov, J. Wang, J. Muhammad, J.M. Patti, and G. Henson Design, synthesis and evaluation of a novel double prodrug: INX-08189. A new clinical candidate for hepatitis C virus Bioorg. Med. Chem. Lett. 20 2010 4850 4854
33. K.A. Nieforth, P.N. Morcos, L. Chang, B. Davies, R. Li, and P.F. Smith Safety, pharmacokinetics (PK), and antiviral activity of RG7348, a novel hepdirecttm liver-targeted double prodrug hepatitis C virus (HCV) nucleotide polymerase inhibitor Clin. Pharmacol. Ther. 91 2012 S96 S135
34. A. Osinusi, E.G. Meissner, Y.J. Lee, D. Bon, L. Heytens, A. Nelson, M. Sneller, A. Kohli, L. Barrett, M. Proschan, E. Herrmann, B. Shivakumar, W. Gu, R. Kwan, G. Teferi, R. Talwani, R. Silk, C. Kotb, S. Wroblewski, D. Fishbein, R. Dewar, H. Highbarger, X. Zhang, D. Kleiner, B.J. Wood, J. Chavez, W.T. Symonds, M. Subramanian, J. McHutchison, M.A. Polis, A.S. Fauci, H. Masur, and S. Kottilil Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial JAMA 310 2013 804 811
35. Patti, J.M.; Matson, M.; Goehlecke, B.; Barry, A.; Wensel, E.; Pentikis, H.; Alam, J.; Henson, G.; 2011. A study of the safety and pharmacokinetics of single ascending oral doses of INX-08189, a nucleotide polymerase inhibitor, in healthy subjects. In: Paper presented at the 46th Annual Meeting of the European Association for the Study of the Liver, Berlin, Germany.
36. S. Pol, A. Vallet-Pichard, and M. Corouge Treatment of hepatitis C virus genotype 3-infection Liver Int. 34 Suppl. 1 2014 18 23
37. Popa, S.; Berliba, A.; Ghicavil, N.; Patat, A.A.; Kauffman, R.S.; Krop, J.; Garg, V.; Tong, M.; Chanda, S.M.; Zhang, Q.; 2013. VX-135, a once-daily nucleotide HCV polymerase inhibitor, was well tolerated and demonstrated potent antiviral activity when given with ribavirin in treatment-naive patients with genotype 1 HCV. In: Paper presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC.
38. P.G. Reddy, D. Bao, W. Chang, B.K. Chun, J. Du, D. Nagarathnam, S. Rachakonda, B.S. Ross, H.R. Zhang, S. Bansal, C.L. Espiritu, M. Keilman, A.M. Lam, C. Niu, H.M. Steuer, P.A. Furman, M.J. Otto, and M.J. Sofia 2′-Deoxy-2′-alpha-fluoro-2′-beta-C-methyl 3′,5′- cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: discovery of PSI-352938 Bioorg. Med. Chem. Lett. 20 2010 7376 7380
39. M. Rodriguez-Torres, E. Lawitz, K.V. Kowdley, D.R. Nelson, E. Dejesus, J.G. McHutchison, M.T. Cornpropst, M. Mader, E. Albanis, D. Jiang, C.M. Hebner, W.T. Symonds, M.M. Berrey, and J. Lalezari Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naive patients with HCV genotype 1: a randomized, 28-day, dose-ranging trial J. Hepatol. 58 2013 663 668
40. R. Schinazi, P. Halfon, P. Marcellin, and T. Asselah HCV direct-acting antiviral agents: the best interferon-free combinations Liver Int. 34 Suppl. 1 2014 69 78
41. M.J. Sofia Nucleotide prodrugs for the treatment of HCV infection Adv. Pharmacol. 67 2013 39 73
42. M.J. Sofia, D. Bao, W. Chang, J. Du, D. Nagarathnam, S. Rachakonda, P.G. Reddy, B.S. Ross, P. Wang, H.R. Zhang, S. Bansal, C. Espiritu, M. Keilman, A.M. Lam, H.M. Steuer, C. Niu, M.J. Otto, and P.A. Furman Discovery of a beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus J. Med. Chem. 53 2010 7202 7218
43. M.J. Sofia, W. Chang, P.A. Furman, R.T. Mosley, and B.S. Ross Nucleoside, nucleotide and non-nucleside inhibitors of hepatitis D virus NS5B RNA-dependent RNA polymerase J. Med. Chem. 55 2012 2481 2531
44. M.J. Sofia, P.A. Furman, and W.T. Symonds 2′-F-2′-C-methyl nucleosides and nucleotides for the treatment of hepatitis C virus: from discovery to the clinic J.C. Barrish, P.H. Carter, P.T.W. Cheng, R. Zahler, RSC Drug Discovery Ser. Accounts in Drug Discovery 4 2010 Royal Society of Chemistry UK 238 266
45. Staton, T.; 2014. Gilead in Talks with Indian Drugmakers to sell Sovaldi at Cut-Rate Prices. Retrieved April 11, from < http://www.fiercepharma.com/ story/gilead-talks-indian-drugmakers-sell-sovaldi-cut-rate-prices/2014-02-04 >.
46. M.S. Sulkowski, D.F. Gardiner, M. Rodriguez-Torres, K.R. Reddy, T. Hassanein, I. Jacobson, E. Lawitz, A.S. Lok, F. Hinestrosa, P.J. Thuluvath, H. Schwartz, D.R. Nelson, G.T. Everson, T. Eley, M. Wind-Rotolo, S.P. Huang, M. Gao, D. Hernandez, F. McPhee, D. Sherman, R. Hindes, W. Symonds, C. Pasquinelli, and D.M. Grasela Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection N. Engl. J. Med. 370 2014 211 221
47. E.B. Tapper, and N.H. Afdhal Is 3 the new 1: perspectives on virology, natural history and treatment for hepatitis C genotype 3 J. Viral Hepatitis 20 2013 669 677
48. X. Tong, S. Le Pogam, L. Li, K. Haines, K. Piso, V. Baronas, J.M. Yan, S.S. So, K. Klumpp, and I. Najera In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir J. Infect. Dis. 209 2014 668 675
49. Yang, W.; Wiles, J.; Patel, D.; Podos, S.; Fabrycki, J.; Zhao, Y.; Jia, L.; Yang, G.; Rivera, J.; Elliot, M.; Marlor, C.; Wang, X.; Chen, D.; Wang, Q.; Deshpande, M.; 2013. Preclinical characteristics of ACH-3422: a potent uridine nucleotide prodrug for inhibition of hepatitis C virus NS5B RNA polymerase. In: Paper presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC. Abst # 475.
50. Zennou, V.; Lam, A.M.; Keilman, M.; Espiritu, C.; Micolochick Steuer, H.; Sofia, M.J.; Reddy, P.G.; Chang, W.; Rachakonda, S.; Otto, M.J.; Furman, P.A.; 2010. Combination of two complementary nucleotide analogues, PSI-7977 and PSI-938, effectively clears wild type and NS5B:S282T HCV replicons-comparison with combinations of other antiviral compounds. In: Paper presented at the 61st Annual Meeting of the European Association for the Study of the Liver, Vienna, Austria.
51. Zeuzem, S.; Nelson, D.; Andreone, P.; Ferenci, P.; Herring, R.; Jensen, D.; Marcellin, P.; Pockros, P.; Rodriguez-Torres, M.; Rossaro, L.; Rustgi, V.; Sepe, T.; Sulkowski, M.; Thomason, I.; Yoshida, E.; Chan, A.; Hill, G.; 2010. Phase iib study of balapiravir (RG1626; nucleoside analogue inhibitor of HCV polymerase) plus peginterferon alfa-2a (40kD) and ribavirin for chronic hepatitis C genotype 1: final results. In: Paper presented at the 45th Annual Meeting of the European Association for the Study of the Liver, Vienna, Austria.
52. X.J. Zhou, K. Pietropaolo, J. Chen, S. Khan, J. Sullivan-Bolyai, and D. Mayers Safety and pharmacokinetics of IDX184, a liver-targeted nucleotide polymerase inhibitor of hepatitis C virus, in healthy subjects Antimicrob. Agents Chemother. 55 2011 76 81