New direct-acting antivirals in hepatitis C therapy: A review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir

Expert Review of Clinical Pharmacology

Volumn 9, Issue 2, 2016, Pages 287-302

  McConachie, Sean M ^a   Wilhelm, Sheila M ^b,c   Kale Pradhan, Pramodini B ^b,d  

^a DeKalb Medical Center   (United States)

^b WAYNE STATE UNIVERSITY   (United States)

^c HARPER UNIVERSITY HOSPITAL   (United States)

^d ST JOHN HOSPITAL AND MEDICAL CENTER   (United States)

Author keywords

daclatasvir; dasabuvir; Hepatitis C; ledipasvir; ombitasvir; paritaprevir; simeprevir; sofosbuvir; sustained virologic response; virologic relapse

Indexed keywords

ANTACID AGENT; ANTICONVULSIVE AGENT; ANTIFUNGAL AGENT; ANTIVIRUS AGENT; BILIRUBIN; BOCEPREVIR; CALCINEURIN INHIBITOR; CARBAMAZEPINE; CYCLOSPORIN; DACLATASVIR; DASABUVIR; DASABUVIR PLUS OMBITASVIR PLUS PARITAPREVIR PLUS RITONAVIR; DEXAMETHASONE; HEMOGLOBIN; HISTAMINE H2 RECEPTOR ANTAGONIST; HYPERICUM PERFORATUM EXTRACT; LEDIPASVIR; LEDIPASVIR PLUS SOFOSBUVIR; PHENYTOIN; PROTON PUMP INHIBITOR; RIFAMPICIN; RITONAVIR; SIMEPREVIR; SOFOSBUVIR; TELAPREVIR; TIPRANAVIR; TRIACYLGLYCEROL LIPASE;

ANEMIA; AREA UNDER THE CURVE; ASTHENIA; CLINICAL PHARMACOLOGY; CONCENTRATION AT STEADY-STATE; DIARRHEA; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; DYSPNEA; FATIGUE; GENOTYPE; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HEPATITIS C; HUMAN; HYPERBILIRUBINEMIA; INSOMNIA; IRRITABILITY; MAXIMUM PLASMA CONCENTRATION; MYALGIA; NAUSEA; OUTCOME ASSESSMENT; PHARMACODYNAMICS; PHOTOSENSITIVITY; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; REVIEW; SIDE EFFECT; TREATMENT RESPONSE; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; ANTIVIRAL RESISTANCE; COMBINATION DRUG THERAPY; DRUG APPROVAL; DRUG EFFECTS; HEPATITIS C, CHRONIC; PRACTICE GUIDELINE; VIRUS REPLICATION;

ANTIVIRAL AGENTS; DRUG APPROVAL; DRUG RESISTANCE, VIRAL; DRUG THERAPY, COMBINATION; HEPATITIS C, CHRONIC; HUMANS; PRACTICE GUIDELINES AS TOPIC; VIRUS REPLICATION;

EID: 84958608308     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/17512433.2016.1129272     Document Type: Review

References (85)

1. Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: A global overview. Clin Liver Dis. 2010;14(1):1-21, vii
2. WHO hepatitis C fact sheet, No 164. [Internet]; [updated 2015 Jul; cited 2015 Dec 1]. Available from: http://www. who.int/mediacentre/factsheets/fs164/en/
3. Denniston MM, Jiles RB, Drobeniuc J. Chronic hepatitis C virus infection in the United States, national health and nutrition examination survey 2003 to 2010. Ann Intern Med. 2014;160(5):293-300
4. Screening for hepatitis C virus infection in adults clinical summary of U.S. preventive services task force recommendation; 2013 [cited 2015 Dec 1]. Available from: http://www.uspreventiveservicestaskforce.org/Page/ Document/UpdateSummaryFinal/hepatitis-c-screening
5. Hepatitis C information for healthcare professionals [Internet]. Center for Disease Control and Prevention. US Department of Health and Human Services; 2015 [cited 2015 Oct 14]. Available from: http://Www.Cdc.Gov/ Hepatitis/Hcv/Hcvfaq.Htm
6. Sangiovanni A, Prati GM, Fasani P, et al. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology. 2006;43(6):1303-1310
7. Gentile I, Coppola N, Pasquale G, et al. A simple noninvasive score based on routine parameters can predict liver cirrhosis in patients with chronic hepatitis C. Hepat Mon. 2013;13(5):e8352
8. AASLD guidelines: AASLD/IDSA/IAS-USA. Recommendations for testing, managing, and treating hepatitis C; [cited 2015 Dec 1]. Available from: http:// www.hcvguidelines.org
9. Jazwinski A, Muir AJ. Direct-acting antiviral medications for chronic hepatitis C virus infection. Gastroenterol Hepatol. 2011;7(3):154-162
10. Ge D, Fellay J, Thompson A. Genetic variation in Il28b predicts hepatitis C treatment-induced viral clearance. Nat Rev Gastroenterol Hepatol. 2009;461:399-401
11. Poynard T, Mchutchinson J, Goodman Z, et al. Is an ''a La Carte'' combination interferon Alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C Hepatology. 2000;31:211-218
12. Ismail MH. Prediction of sustained virologic responses to combination therapy of pegylated interferon- and ribavirin in patients with chronic hepatitis C infection. J Family Community Med. 2013;20(1):35-40
13. Parfieniuk A, Jaroszewicz J, Flisiak R. Specifically targeted antiviral therapy for hepatitis C virus. World J Gastroenterol. 2007;13(43):5673-5681
14. Pegasys [Package Insert]. South San Francisco, CA: Hoffmann-La Roche Inc; 2002 [reviced 2014 sep; cited Dec 1 2015]. Available from: http://www.accessdata.fda. gov/drugsatfda-docs/label/2002/pegihof101602lb.htm
15. Rebetol [Package Insert]. Whitehouse Station, NJ: Merck & Co Inc; 1998 [reviced Dec 2014; cited Dec 1 2015]. Available from: https://www.merck.com/product/usa/pi- circulars/r/rebetol/rebetol-pi.pdf
16. Victrelis [Package Insert]. Whitehouse Station, NJ: Merck & Co Inc; 2011 [revised 2011 may; cited 2015 Dec 2]. Available from: https://www.merck.com/product/usa/pi- circulars/v/victrelis/victrelis-pi.pdf
17. Incivek [Package Insert]. Cambridge, MA: Vertex Pharmaceuticals Inc; 2011 [revised 2012 Dec; cited 2015 Dec 2]. Available from: http://pi.vrtx.com/files/uspi-tela previr.pdf
18. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV 1 infection. N Engl J Med. 2011;364(13):1207-1217
19. Poordad F, Mccone J, Bacon B, et al. Boceprevir for untreated chronic HCV 1 infection. N Engl J Med. 2011;364(13):1195-1206
20. Zeuzem S, Andreone P, Pol S, et al. Telapravir for retreatment of HCV infection. N Engl J Med. 2011;364(25):2417-2428
21. Jacobson IM, Mchutchinson JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405-2416
22. Ghany MG, Nelson DR, Strader DB, et al. American association for study of liver diseases, an update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the study of liver diseases. Hepatology. 2011;54(4):1433-1444
23. Lindenbach BD, Rice CM. Unravelling hepatitis C virus replication from genome to function. Nature. 2005;436 (7053):933-938
24. Bartenschlager R, Lohmann V, Penin F. The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection. Nat Rev Microbiol. 2013;11(7):482-496
25. Schinazi R, Halfon P, Marcellin P, et al. HCV direct-acting antiviral agents: The best interferon-free combinations. Liver Int. 2014;34(Suppl. 1):69-78
26. Kumar S, Jacobson IM. Antiviral therapy with nucleotide polymerase inhibitors for chronic hepatitis C. J Hepatol. 2014;61(1 Suppl):S91-7
27. Berger C, Romero-Brey I, Radujkovic D, et al. Daclatasvirlike inhibitors of NS5a block early biogenesis of hepatitis c virus-induced membranous replication factories, independent of RNA replication. Gastroenterology. 2014;147 (5):1094-105 e25
28. Gao M. Antiviral activity and resistance of HCV NS5a replication complex inhibitors. Curr Opin Virol. 2013;3 (5):514-520
29. Eyre NS, Beard MR. HCV NS5a inhibitors disrupt replication factory formation: A novel mechanism of antiviral action. Gastroenterology. 2014;147(5):959-962
30. Nakamoto S, Kanda T, Wu S, et al. Hepatitis C virus NS5a inhibitors and drug resistance mutations. World J Gastroenterol. 2014;20(11):2902-2912
31. Sovaldi [Package Insert]. Foster City, CA: Gilead Sciences Inc; 2013 [revised 2014 Nov; cited 2015 Dec 2]. Available from: http://www.gilead.com/~/media/Files/pdfs/medi cines/liver-disease/sovaldi/sovaldi-pi.pdf
32. Keating GM, Vaidya A. Sofosbuvir: first global approval. Drugs. 2014;74(2):273-282
33. Koff RS. 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. 2014;39(5):478-487
34. Tong X, Le Pogam S, Li L, et al. 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. 2014;209 (5):668-675
35. Kirby BJ, Symonds WT, Kearney BP, et al. Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis C virus NS5b polymerase inhibitor sofosbuvir. Clin Pharmacokinet. 2015;54 (7):677-690
36. Harvoni [Package Insert]. Foster City, CA: Gilead Sciences Inc; 2014 [revised 2014 Oct; cited 2015 Feb 12]. Available from: https://www.gilead.com/~/media/Files/pdfs/medi cines/liver-disease/harvoni/harvoni-pi.pdf
37. Gentile I, Buonomo AR, Borgia F. Ledipasvir: A novel synthetic antiviral for the treatment of HCV infection. Expert Opin Investig Drugs. 2014;23(4):561-571
38. Olysio [Package Insert]. Titusville, NJ: Janssen Therapeutics; 2013 [revised 2014 Nov; cited 2015 Feb 12]. Available from: https://www.olysio.com/shared/pro duct/olysio/prescribing-information.pdf
39. Daklinza [Package Insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2015 [revised 2015 Jul 24; cited 2015 Dec 2]. Available from: Packageinserts.Bms.Com/Pi/Pi- Daklinza.Pdf
40. Viekira Pak [Package Insert]. North Chicago, IL: Abbvie Inc; 2014 [revised Feb 2015; cited 2015 Dec 2]. Available from: http://Www.Accessdata.Fda.Gov/Drugsatfda-Docs/ Label/2014/206619lbl.Pdf
41. Klibanov OM, Gale SE, Santevecchi B. Ombitasvir/paritaprevir/ ritonavir and dasabuvir tablets for hepatitis C virus genotype 1 infection. Ann Pharmacother. 2015;49 (5):566-581
42. Smith MA, Regal RE, Mohammad RA. Daclatasvir: A NS5a replication complex inhibitor for hepatitis C infection. Ann Pharmacother. 2016;50(1):39-46
43. Tischer S, Fontana RJ. Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting. J Hepatol. 2014;60(4):872-884
44. Kiser JJ, Burton JR Jr, Everson GT. Drug-drug interactions during antiviral therapy for chronic hepatitis C. Nat Rev Gastroenterol Hepatol. 2013;10:596-606
45. Rodriguez-Torres M, Lawitz E, Kowdley KV, et al. Sofosbuvir (Gs-7977) plus peginterferon/ribavirin in treatment-naive patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial. J Hepatol. 2013;58(4):663-668
46. Gane EJ, Stedman CA, Hyland RH, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368(1):34-44
47. Lawitz E, Lalezari JP, Hassanein T, 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, doubleblind, phase 2 trial. Lancet Infect Dis. 2013;13(5):401-408
48. Kowdley KV, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatmentnaive patients with hepatitis C genotype-1 infection (atomic): An open-label, randomised, multicentre phase 2 trial. Lancet. 2013;381(9883):2100-2107
49. Lawitz EJ, Rodriguez-Torres M, Denning J, et al. All-oral therapy with nucleotide inhibitors sofosbuvir and gs-0938 for 14 days in treatment-naive genotype 1 hepatitis C (Nuclear). J Viral Hepat. 2013;20(10):699-707
50. Sulkowski MS, Naggie S, Lalezari J, et al. Sofosbuvir and ribavirin for hepatitis C in patients with hiv coinfection. JAMA. 2014;312(4):353-361
51. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117
52. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of hcv infection after liver transplantation: An open-label study. Gastroenterology. 2015;148(1):100-107 e1
53. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878-1887
54. Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368(20):1867-1877
55. Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370(21):1993-2001
56. Lawitz E, Poordad FF, Pang PS, et al. 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. 2014;383 (9916):515-523
57. Osinusi A, Kohli A, Marti MM, et al. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: An open-label pilot study. Ann Intern Med. 2014;161(9):634-638
58. Kohli A, Osinusi A, Sims Z, et al. Virological response after 6 week triple-drug regimens for hepatitis C: A proof-ofconcept phase 2a cohort study. Lancet. 2015;385 (9973):1107-1113
59. Wyles DL, Rodriguez-Torres M, Lawitz E, et al. All-oral combination of ledipasvir, vedroprevir, tegobuvir, and ribavirin in treatment-naive patients with genotype 1 HCV infection. Hepatology. 2014;60(1):56-64
60. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898
61. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493
62. Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879-1888
63. Kowdley KV, An D, Pang PS, et al. Analysis of subgroup differences in the ion-3 trial of ledipasvir-sofosbuvir in chronic hepatitis C infection. Open Forum Infect Dis. 2015;2(2):ofv056
64. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370(3):211-221
65. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: Ally-3 phase iii study. Hepatology. 2015;61(4):1127-1135
66. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725
67. Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in nonresponders to pegylated interferon and ribavirin and treatment-naive patients: The cosmos randomised study. Lancet. 2014;384(9956):1756-1765
68. Jacobson IM, Dore GJ, Foster GR, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatmentnaive patients with chronic hepatitis C virus genotype 1 infection (Quest-1): A phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014;384(9941):403-413
69. Manns M, Marcellin P, Poordad F, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (quest-2): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014;384 (9941):414-426
70. Forns X, Lawitz E, Zeuzem S, et al. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 Who relapsed after previous therapy: A phase 3 trial. Gastroenterology. 2014;146 (7):1669-79 e3
71. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with Abt-450/R-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1594-1603
72. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with Abt-450/R-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370(17):1604-1614
73. Ferenci P, Bernstein D, Lalezari J, et al. Abt-450/R-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370(21):1983-1992
74. Poordad F, Hezode C, Trinh R, et al. Abt-450/R-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370(21):1973-1982
75. Kwo PY, Mantry PS, Coakley E, et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;371(25):2375-2382
76. Ohkoshi S, Hirono H, Yamagiwa S. Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis. World J Gastrointest Pharmacol Ther. 2015;6(4):114-119
77. Righi E, Londero A, Carnelutti A, et al. Impact of new treatment options for hepatitis C virus infection in liver transplantation. World J Gastroenterol. 2015;21 (38):10760-10775
78. Carvalho-Filho RJ, Feldner AC, Silva AE, et al. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422
79. Del Bello D, Ita Nagy F, Hand J, et al. Direct-acting antiviralbased therapy for chronic hepatitis C virus in HIV-infected patients. Curr Opin HIV AIDS. 2015;10(5):337-347
80. Najafzadeh M, Andersson K, Shrank WH, et al. Costeffectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med. 2015;162(6):407-419
81. Walker J. Expensive hepatitis C medications drive prescription-drug spending. The Wall Street Journal. 2015 Mar 10 [cited 2015 Aug 26]. Available from: http://www. wsj.com/articles/expensive-hepatitis-c-medicationsdrive-prescription-drug-spending-1425960214
82. De Clercq E. current race in the development of Daas (Direct-Acting Antivirals) against HCV. Biochem Pharmacol. 2014;89(4):441-452
83. Hill A, Cooke G. Hepatitis C can be cured globally, but at what cost Science. 2014;345(6193):141-142
84. Cohen J. advocates protest the cost of a hepatitis C cure. Science. 2013;342:1302-1303
85. Steinbrook R, Redberg R. The high price of the new hepatitis C virus drugs. JAMA Intern Med. 2014;174 (7):1172.