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•• Halfon P, Sarrazin C. Future treatment of chronic hepatitis C with direct acting antivirals: is resistance important? Liver Int 2012;32:79–87. The authors examine the major resistant point mutations for the NS3 HCV protease region, as well as the NS5B polymerase, and most important to this paper, the NS5A region.
McPhee F, Hernandez D, Yu F, et al. Characterization of virologic escape in HCV genotype 1 null responders receiving a combination of the NS3 protease inhibitor BMS-650032 and NS5A inhibitor BMS-790052. J Hepatol. 2011;54:28–9.CrossRef
• Fridell RA, Qiu D, Wang C, Valera L, Gao M.: Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob Agents Chemother 2010, 54:3641–3650. The authors perform resistance testing characterizing escape variants of the NS5A inhibitor BMS 790052 in a replicon system.
Pol S, Everson G, Ghalib R, et al. Once-daily NS5A inhibitor (BMS 790052) plus peginterfeon-alpha-2A and ribavirin produces high rates of extended rapid virological response in treatment-naïve HCV-genotype 1 subjects: phase 2A trial. J Hepatol. 2010;52:S462.CrossRef
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Ratziu V, Gadano A, Pol S, Hezode C, et al. Triple therapy with Daclatasvir (DCV; BMS-790052), peginterferon alfa-2a and ribavirin in HCV-infected prior null and partial responders: 12-week results of phase 2b COMMAND-2 Trial. Presented at 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain; April 18–22, 2012.
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•• Gane E, Roberts S, Stedman C, et al.: Interferon-free oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and protease inhibitor (danoprevir/RG7227) for the treatment of chronic hepatitis C genotype 1 infection: results of the INFORM-1 trial. Lancet 2010;376:1467–1475. A very important report of the first interferon-free oral combination therapy for treatment of chronic hepatitis C.
•• Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 2012;366:216–224. Again, a very exciting study of the combination of two oral DAA’s against chronic hepatitis C. In particular, this was a protease inhibitor asunaprevir in combination with daclatasvir, a NS5A inhibitor. The two oral DAA’s were used together, as well in quadruple therapy with a pegylated interferon and ribavirin for the treatment of non-responders to prior interferon and ribavirin therapy.
•• Chayama K, Takahashi S, Toyota J, et al. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b–infected null responders. Hepatology 2012;3:742–748. This is a somewhat similar study to the above, however, in a Japanese population. Very impressive efficacy reported by the authors.
Sulkowski M, Gardiner D, Lawitz E, Hinestrosa F, et al. Potent viral suppression with the all-oral combination of Daclatasvir (NS5A inhibitor) and GS-7977 (nucleotide NS5B inhibitor), +/- ribavirin, in treatment-naive patients with chronic HCV GT1, 2, or 3 (100 % SVR gt1, 91 % gt2). Presented at 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain; April 18–22, 2012.
Dumas E, Lawal A, Menon R.M, Podsadecki T, et al. Pharmacokinetics, safety and tolerability of the HCV NS5A inhibitor ABT-267 following single and multiple doses in healthy adult volunteers. Presented at 46th Annual Meeting of the European Association for the Study of the Liver. Berlin, Germany; March 30-April 3rd 2011.
Clinical Trials Gov. Study of ABT-267 in Treatment Naïve Hepatitis C Virus (HCV) Genotype 1 Infected Subjects. Available at http://clinicaltrials.gov/ct2/show/NCT01314261
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Sullivan JG, Rodriguez-Torres M, Lawitz E, Poordad F, et al. ABT-267 combined with pegylated interferon alpha-2a/ribavirin in genotype 1 (GT1) HCV-infected treatment-naïve subjects: 12-week antiviral and safety analysis. Presented at 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain; April 18–22, 2012.
National Aids Treatment Advocacy Project. A study to evaluate the efficacy, safety, and pharmacokinetics of ABT-450 with ritonavir (ABT-450/r) when given together with ABT-333 and Ribavirin (RBV) in treatment-naïve and non-responder subjects with genotype 1 chronic hepatitis C virus (HCV) infection. Available at http://clinicaltrials.gov/ct2/show/NCT01306617?cond=%22Hepatitis+C%22&rank=2
. Accessed March 2012.
Achillion Announces Preliminary Phase 1b Proof-of-Concept Data with ACH-2928 NS5A Inhibitor for the Treatment of Hepatitis C. Available at http://ir.achillion.com/releasedetail.cfm?ReleaseID=629849
. Accessed March 2012.
National Aids Treatment Advocacy Project. Achillion Announces Nomination of Second Generation NS5A Inhibitor for the Treatment of Hepatitis C. Available at http://www.natap.org/2011/HCV/101311_01.htm
. Accessed February 2012.
National Aids Treatment Advocacy Project. Enanta’s Lead NS5A Inhibitor Candidate for HCV, EDP-239, Selected as One of Windhover’s Top 10 Infectious Disease Projects to Watch. Available at www.natap.org/2010/HCV/030410_02.htm
. Accessed March 2012.
Lawitz E, Gruener D, Hill J, et al. A phase 1, randomized, placebo-controlled, three-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C. J Hepatol 2012; [Epub ahead of print]
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Sulkowski M, Rodriguez-Torres M, Lawitz E, Shiffman M, et al. Gilead: Interim sustained virologic response rates in treatment-naïve HCV genotype 1a and 1b patients treated for 12 or 24 weeks with an interferon-free all-oral quad regimen. Presented at 47th Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain; April 18–22, 2012.
National Aids Treatment Advocacy Project. Nomination of Second Generation NS5A Inhibitor for the Treatment of Hepatitis C. Available at http://www.natap.org/2011/HCV/101311_01.htm
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National Aids Treatment Advocacy Project. Idenix Update Slides—IDX184 Nucleotide, new IDX719 NS5A (slides attached from investor call this morning), 2 new nucleotides in development. Available at http://www.natap.org/2012/HCV/010912_03.htm
. Accessed March 2012
Idenix Pharmaceuticals. Idenix Announces Positive Clinical Data for HCV Drug Candidates IDX184 and IDX719. Available at http://ir.idenix.com/releasedetail.cfm?ReleaseID=684347
Accessed June 2012
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National Aids Treatment Advocacy Project. Dose-Ranging Trial of PPI-461, a Potent New Pan-Genotypic HCV NS5A Inhibitor, in Patients with HCV Genotype-1 Infection. Available at http://www.natap.org/2011/AASLD/AASLD_10.htm
Accessed March 2012
Presido Pharmaceuticals Inc. Clinical Proof-of-Concept Data for its First HCV NS5A Inhibitor, PPI-461, and Initiation of Clinical Testing for its Second-Generation NS5A Inhibitor, PPI-668. Available at http://www.presidiopharma.com/docs/Presidio%20Pharmaceuticals%20Announces%20Clinical%20POC%20Data-PPI-461%20%20Initiation%20of%20Clinical%20Studies%20of%20PPI-668%20Press%20Release%20November%204%202011.pdf
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