RG7128, a prodrug of PSI-6130
Presentations
Sustained Virologic Response following RG7128 1500 mg BID PEG-IFN/RBV for 28 days in HCV Genotype 2/3 prior non-responders
EJ Gane et al
45th Annual Meeting of the European Association for the Study of the Liver (EASL)
Vienna, Austria
Apr 14-Apr 18, 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.
V. Zennou et al
45th Annual Meeting of the European Association for the Study of the Liver (EASL)
Vienna, Austria
Apr 14-Apr 18, 2010
Combination Therapy with a Nucleoside Polymerase (RG7128) and Protease (RG7227/ITMN-191) Inhibitor In HCV: Safety, Pharmacokinetics, and Virologic Results from INFORM-1
E. Gane et al
60th Annual Meeting of the American Association for the Study of Liver Diseases
Boston, MA
Oct 30-Nov 3, 2009
Combination Therapy with Nucleoside Polymerase (RG7128) and Protease (RG7227) Inhibitors in Genotype 1 HCV Infected Patients: Interim Resistance Analysis of INFORM-1 Cohorts A–D
S. Le Pogam et al
60th Annual Meeting of the American Association for the Study of Liver Diseases
Boston, MA
Oct 30-Nov 3, 2009
Pharmacokinetics/Pharmacodynamics (PK/PD) of Combination RG7227 and RG7128 Therapy from INFORM-1 Demonstrates Similar Early HCV Viral Dynamics when RG7227 is Combined with either Peg-IFN/ribavirin (SoC) or RG7128
P.N. Morcos et al
60th Annual Meeting of the American Association for the Study of Liver Diseases
Boston, MA
Oct 30-Nov 3, 2009
No Evidence of R7128 Drug Resistance After Up To 4 Weeks Treatment of GT1,2 and 3 Hepatitis C Virus Infected Individuals.
S Le Pogam et al
44th Annual Meeting of the European Association for the Study of the Liver (EASL)
Copenhagen, Denmark
Apr 22-Apr 26, 2009
Combination of the NS3/4A Protease Inhibitor ITMN-191 (R7227) with the Active Moiety of the NS5B Inhibitors R1626 or R7128 Enhances Replicon Clearance and Reduces the Emergence of Drug Resistant Variants
H. Tan et al
59th Annual Meeting of the American Association for the Study of Liver Diseases
San Francisco, CA
Oct 31 – Nov 4, 2008
Phase I Subanalysis Cohorts 1, 2, 3
Potent Antiviral Response To The HCV Nucleoside Polymerase Inhibitor R7128 For 28 Days With Peg-IFN And Ribavirin: Subanalysis by Race/Ethnicity, Weight and HCV Genotype
M. Rodriguez-Torres et al.
The 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
San Francisco, California, USA
Oct 31-Nov 4, 2008
Phase I Analysis Cohort 4
Antiviral Activity Of The HCV Nucleoside Polymerase Inhibitor R7128 In HCV Genotype 2 and 3 Prior Non-Responders: Results Of R7128 1500mg BID With PEG-IFN And Ribavirin For 28 Days
E. Gane et al
The 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
San Francisco, California, USA
Oct 31-Nov 4, 2008
In Vitro Combination with ITMN-191
Combination of the NS3/4A Protease Inhibitor ITMN-191 (R7227) with the Active Moiety of the NS5B Inhibitors R1626 or R7128 Enhances Replicon Clearance and Reduces the Emergence of Drug Resistant Variants.
H. Tan et al.
The 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
San Francisco, California, USA
Oct 31-Nov 4, 2008
Phase 1 Combination Cohorts 1 and 2
Potent Antiviral Activity of the HCV Nucleoside Polymerase Inhibitor, R7128, in Combination with PEG-IFN alfa-2a and Ribavirin.
McHutchison, et al.
43rd Annual Meeting of the European Association for the Study of the Liver (EASL)
Milan, Italy
April 23-27, 2008
Phase 1 Overview
Potent Antiviral Activity of the Nucleoside HCV Inhibitor, R7128, in Prior IFN Non-Responders.
JG McHutchison, et al.
Frontiers in Drug Development in Viral Hepatitis (HEP-DART)
Lahaina, Hawaii
December 9 - 13, 2007
Phase 1 Multiple Ascending Dose Study
Antiviral Activity, Pharmacokinetics, Safety, and Tolerability of R7128, a Novel Nucleoside HCV RNA Polymerase Inhibitor, Following Multiple, Ascending, Oral Doses in Patients with HCV Genotype 1 Infection Who have Failed Prior Interferon Therapy. R. Reddy, et al.
58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
Boston USA
November 2-6, 2007
Phase 1 Single Ascending Dose Study
Pharmacokinetics, Safety, and Tolerability of R7128, a Novel Nucleoside Polymerase Inhibitor for HCV Following Single, Ascending Oral Doses in Healthy Volunteers.
Otto MJ, et al.
14th International Symposium on Hepatitis C Virus and Related Viruses
Glasgow, Scotland
September 9-13, 2007
R7128, A Potent and Selective Nucleoside Inhibitor of HCV NS5B Polymerase: An Overview of Clinical Efficacy and Progress Toward Second Generation Inhibitors
M. Sofia
HCV Drug Discovery 2008
Chicago, IL
April 28, 2008
Preclinical
High Genetic Barrier to HCV Resistance Presented by PSI-6130.
A Uzgiris, et al.
Frontiers in Drug Development in Viral Hepatitis (HEP-DART)
Lahaina, Hawaii
December 9-13, 2007
Preclinical
The Mechanism of Action of Beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine Involves a Second Metabolic Pathway Leading to Beta-D-2'-Deoxy-2'-fluoro-2'-C-methyluridine 5'-Triphosphate, a Potent Inhibitor of the HCV RNA-Dependent RNA Polymerase.
Murakami E, et al (Pharmasset).
14th International Symposium on Hepatitis C Virus and Related Viruses
Glasgow, Scotland
September 9-13, 2007
Preclinical
The Nucleoside Inhibitors R1479, PSI-6130, and NM107 have a Higher Genetic Barrier to Resistance than the Non-nucleoside Inhibitor HCV-796 and the Protease Inhibitor VX-950.
McCown M, et al (Roche Palo Alto).
14th International Symposium on Hepatitis C Virus and Related Viruses
Glasgow, Scotland
September 9-13, 2007
Preclinical
In Vitro Selection and Characterization of HCV Replicons Resistant to PSI-6130.
Ali S, et al (Roche Palo Alto).
14th International Symposium on Hepatitis C Virus and Related Viruses
Glasgow, Scotland
September 9-13, 2007
Preclinical
Inhibition of HCV Replication by PSI-6130: Characterization of Activity in the HCV Replicon System
42nd Annual Meeting of the European Association for the Study of the Liver (EASL)
Barcelona, Spain
April 11-15, 2007
Preclinical
Inhibition of HCV Replication by PSI-6130: Mechanism of Biochemical Activation and Inhibition
42nd Annual Meeting of the European Association for the Study of the Liver (EASL)
Barcelona, Spain
April 11-15, 2007
Preclinical
Inhibition of HCV Replication by PSI-6130: Mechanism of Biochemical Activation and Inhibition
1st International Workshop on Hepatitis C Resistance & New Compounds
Boston, MA
October 25-26, 2006
Preclinical
Inhibition of HCV Replication by PSI-6130: Characterization of Activity in the HCV Replicon System
1st International Workshop on Hepatitis C Resistance & New Compounds
Boston, MA
October 25-26, 2006
Publications
Murakami E, Bao H, Ramesh M, McBrayer TR, Whitaker T, Micolochick Steuer HM, Schinazi RF, Stuyver LJ, Obikhod A, Otto MJ, Furman PA. Mechanism of activation of {Beta}-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine and inhibition of hepatitis C virus NS5B RNA polymerase. Antimicrobial Agents and Chemotherapy. February 2007, 51(2):503-509.
Stuyver LJ, McBrayer TR, Thranish PM, Clark J, Hollecker L, Lostia S, Nachman T, Grier J, Bennett MA, Xie M-Y, Schinazi RF, Morrey JD, Julander JL, Furman PA, and Otto MJ. Inhibition of hepatitis C replicon RNA synthesis by β-D-2’-deoxy-2’-fluoro-2’-methylcytidine: A specific inhibitor of hepatitis C virus replication. Antiviral Chemistry and Chemotherapy. 2006, 17: 79-87.
Clark JL, Hollecker L, Mason JC, Stuyver LJ, Tharnish PM, Lostia S, McBrayer TR, Schinazi RF, Watanabe KA, Otto MJ, Furman PA, Stec WJ, Patterson SE, Pankiewicx KW. Design, synthesis, and antiviral activity of 2’-deoxy-2’-fluoro-2’-C-methylcytidine, a potent inhibitor of hepatitis C virus replication. Journal of Medicinal Chemistry. 2005, 48(17): 5504-5508.
Stuyver LJ, McBrayer TR, Whitaker T, Tharnish PM, Ramesh M, Lostia S, Cartee L, Shi, Hobbs A, Schinazi RF, Watanabe KA, Otto MJ. Inhibition of the Subgenomic Heptatitis C Virus Replicon in Huh-7 cells by 2'-Deoxy-2'-Fluorocytidine. Antimicrobial Agents Chemotherapy. February 2004, 48(2):651-654.
Stuyver LJ, McBrayer TR, Tharnish PM, Hassan AEA, Chu CK, Pankiewicz K, Watanabe KA, Schinazi RF, Otto MJ. Dynamics of subgenomic heptatitis C virus replicon RNA levels in huh-7 cells after exposure to Nucleoside Antimetabolites. Journal of Virology. October 2003, 77(19):10689-10694.
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