Next-Generation Regimens. The Future of Hepatitis C Virus Therapy

Clinics in Liver Disease

Volumn 19, Issue 4, 2015, Pages 707-716

  Vizuete, John ^a   Hubbard, Hope ^a   Lawitz, Eric ^a  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

Direct acting antivirals; Genotype 1; Hepatitis C; Resistance associated variants; Second generation

Indexed keywords

ABT 493; ABT 530; AGENTS AFFECTING NUCLEIC ACID METABOLISM; ANTIVIRUS AGENT; ASUNAPREVIR PLUS BECLABUVIR PLUS DACLATASVIR; DACLATASVIR; ELBASVIR PLUS GRAZOPREVIR; GRAZOPREVIR; MICRORNA 122; MICRORNA 122 INHIBITOR; MIRAVIRSEN; MK 3682; MK 8408; NONSTRUCTURAL PROTEIN 5A INHIBITOR; ODALASVIR; PEGINTERFERON; PLACEBO; RG 101; RIBAVIRIN; SOFOSBUVIR; SOFOSBUVIR PLUS VELPATASVIR; UNCLASSIFIED DRUG; 2-(PYRROLIDIN-2-YL)-5-(2-(4-(5-(PYRROLIDIN-2-YL)-1H-IMIDAZOL-2-YL)PHENYL)BENZOFURAN-5-YL)-1H-IMIDAZOLE; 8-CYCLOHEXYL-N-((DIMETHYLAMINO)SULFONYL)-1,1A,2,12B-TETRAHYDRO-11-METHOXY-1A-((3-METHYL-3,8-DIAZABICYCLO(3.2.1)OCT-8-YL)CARBONYL)CYCLOPROP(D)INDOLO(2,1-A)(2)BENZAZEPINE-5-CARBOXAMIDE; ASUNAPREVIR; BENZAZEPINE DERIVATIVE; BENZOFURAN DERIVATIVE; BMS-790052; CARBAMIC ACID DERIVATIVE; FUSED HETEROCYCLIC RINGS; IMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; ISOQUINOLINE DERIVATIVE; MICRORNA; MIRN122 MICRORNA, HUMAN; MK-5172; NS-5 PROTEIN, HEPATITIS C VIRUS; NUCLEIC ACID SYNTHESIS INHIBITOR; PROTEINASE INHIBITOR; QUINOXALINE DERIVATIVE; SULFONAMIDE; VELPATASVIR; VIRUS PROTEIN; VIRUS RNA;

ABDOMINAL DISCOMFORT; CHRONIC HEPATITIS C; CONSTIPATION; DEMOGRAPHY; DIARRHEA; DRUG RESPONSE; FATIGUE; GENOTYPE; HEADACHE; HEPATITIS C VIRUS; HUMAN; INJECTION SITE REACTION; LIVER CIRRHOSIS; LIVER FIBROSIS; NAUSEA; REVIEW; SINGLE DRUG DOSE; TREATMENT DURATION; WEAKNESS; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; COMBINATION DRUG THERAPY; DRUG DEVELOPMENT; FORECASTING; GENETICS; HEPACIVIRUS; HEPATITIS C, CHRONIC; MOLECULARLY TARGETED THERAPY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC);

ANTIVIRAL AGENTS; BENZAZEPINES; BENZOFURANS; CARBAMATES; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG DISCOVERY; DRUG THERAPY, COMBINATION; FORECASTING; HEPACIVIRUS; HEPATITIS C, CHRONIC; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; IMIDAZOLES; INDOLES; ISOQUINOLINES; MICRORNAS; MOLECULAR TARGETED THERAPY; NUCLEIC ACID SYNTHESIS INHIBITORS; PROTEASE INHIBITORS; QUINOXALINES; RNA, VIRAL; SOFOSBUVIR; SULFONAMIDES; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84943586630     PISSN: 10893261     EISSN: 15578224     Source Type: Journal    
DOI: 10.1016/j.cld.2015.06.009     Document Type: Review

References (26)

1. Poordad F, Sievert W, Mollison L, et al. All-oral, fixed-dose combination therapy with daclatasvir/asunaprevir/beclabuvir for non-cirrhotic patients with chronic HCV genotype 1 infection: UNITY-1 phase 3 SVR-12 results [LB-7]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 10, 2014.
2. 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, 370:1983-1992.
3. Muir AJ, Poordad F, Lalezari J, et al. All-oral, fixed-dose combination therapy with daclatasvir/asunaprevir/beclabuvir ± ribavirin, for patients with chronic HCV genotype 1 infection and compensated cirrhosis: UNITY-2 phase 3 SVR12 results [LB-2]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 10, 2014.
4. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week combination treatment with daclatasvir (DCV) and sofosbuvir (SOF) in patients infected with HCV genotype (GT) 3: ALLY-3 phase 3 study [LB-2]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
5. Sulkowski M.S., Gardiner D.F., Rodriguez-Torres M., et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014, 370:211-221.
6. Zeuzem S., Dusheiko G.M., Salupere R., et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014, 370:1993-2001.
7. Lawitz E., Mangia A., Wyles D., et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013, 368:1878-1887.
8. Jacobson I.M., Gordon S.C., Kowdley K.V., et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013, 368:1867-1877.
9. Sulkowski M., Hezode C., Gerstoft J., et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2014, 385:1087-1097.
10. Lawitz E., Gane E., Pearlman B., et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2014, 385:1075-1086.
11. Lawitz E, Poordad F, Gutierrez JA, et al. C-SWIFT: grazoprevir (MK-5172)+ elbasvir (MK-8742)+ sofosbuvir in treatment-naive patients with hepatitis C virus genotype 1 infection, with and without cirrhosis, for durations of 4, 6, or 8 weeks (interim Results) [LB-33]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
12. Everson GT, Tran TT, Towner WJ, et al. Safety and efficacy of treatment with the interferon-free, ribavirin-free combination of sofosbuvir+ Gs-5816 for 12 weeks in treatment naive patients with genotype 1-6 HCV infection [abstract 111]. Presented at the 49th annual meeting of the European Association for the Study of the Liver. London, April 11, 2014.
13. Tran TT, Morgan TR, Thuluvath PJ, et al. Safety and Efficacy of treatment with sofosbuvir+ GS-5816+/- ribavirin for 8 or 12 weeks in treatment naive patients with genotype 1-6 HCV infection [abstract: 80]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
14. Muir A, Hill J, Lawitz E, et al. ACH-3102, a second generation NS5A inhibitor, demonstrates potent antiviral activity in patients with genotype 1a HCV infection despite the presence of baseline NS5A-resistant variants [abstract 398]. Presented at the 48th annual meeting of the European Association for the Study of the Liver. Amsterdam, April 27, 2013.
15. Gane EJ, Kocinsky H, Schwabe C, et al. Interim sustained virologic response (SVR), safety and tolerability results of 8-week treatment with ACH-3102 and sofosbuvir in chronic hepatitis C (HCV), genotype-1 (GT-1), treatment-naive patients: a phase 2 "proxy" study [LB-32]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
16. Achillion achieves 100% SVR12 in phase 2 trial evaluating 6-week combination treatment with ACH-3102. 2015. Available at: . Accessed February 11, 2015. http://ir.achillion.com/releasedetail.cfm?releaseid=895306.
17. Lawitz E, O'Riordan WD, Freilich BL, et al. Potent antiviral activity of ABT-493 and ABT-530 with 3-day monotherapy in patients with and without compensated cirrhosis with hepatitis C virus (HCV) genotype 1 infection [abstract 1956]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
18. Gane EJ, Sicard E, Popa S, et al. A phase I/IIa study assessing 7-day dosing of MK-3682 (formerly IDX21437) in subjects infected with hepatitis C virus (HCV) [abstract: 1974]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
19. Asante-Appiah E, Liu R, Curry S, et al. MK-8408, A potent and selective NS5A inhibitor with a high genetic barrier to resistance and activity against HCV genotypes 1-6 [abstract: 1979]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
20. Lahser F, Bystol K, Curry S, et al. The combination of MK-5172, an NS3 inhibitor, and MK-8408, an NS5A inhibitor, presents a high genetic barrier to resistance in HCV genotypes [abstract: 1988]. Presented at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, November 9, 2014.
21. Jopling C.L., Yi M., Lancaster A.M., et al. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 2005, 309:1577-1581.
22. Li Z., Rana T.M. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 2014, 13:622-638.
23. Israelow B., Mullokandov G., Agudo J., et al. Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors. Nat Commun 2014, 18:5408.
24. Janssen H.L., Reesink H.W., Lawitz E.J., et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013, 368:1685-1694.
25. Van der Ree M.H., Van der Meer A.J., de Bruijne J., et al. Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antiviral Res 2014, 111:53-59.
26. All HCV patients treated with a single SC administration of 4 mg/kg of RG-101 responded with mean viral load reduction of 4.8 log10 at Day 29 and 9/14 patients are below the limit of quantification at Day 57. 2015. Available at: . Accessed February 11, 2015. http://ir.regulusrx.com/releasedetail.cfm?ReleaseID-=895314.