NATAP: New HCV Drugs at AASLD Nov 2008

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New HCV Drugs at AASLD Nov 2008from Jules: here are links to NATAP reports from the AASLD liver meeting that are only related to HCV and new drugs with a few additional important HCV reports sprinkled in. At the annual conference which took place in San Francisco from Oct 31-Nov 4 there was quite a lot of new data presented on new HCV drugs which increases now at each new meeting. New data on HCV protease inhibitors and other classes of drugs were reported. The furhest along in development are the 2 new protease inhibitors boceprevir by Schering Plough and telaprevir from Vertex and Tibotec. Both drugs started the final phase, phase III, of development before expected FDA approval. The 2 drugs are being studied in combination with peg+RBV and will be used in combination with these 2 drugs for the forseeable future until a study is completed proving the 2 standard drugs can be eliminated from therapy. Eliminating them from therapy is very debatable as some feel it is possible and some feel it is not possible. Nonetheless we are headed in my opinion to 80% or greater cure rates for all in the future. Upon approval becprevir or telaprevir plus pegRBV should show about 70% SVR rates for some patients but drug resistance is a big concern so for patients with a less than optimal response tp peg/RBV this will have an affect on whether one can or cannot achieve a SVR. Resistance to an HCV protease inhibitor can develop very quickly, within a few days, but the protection of peg/RBV can overcome that if you get a good response to peg/RBV. This issue will be overcome when we can combine 2 or more new oral drugs with or later perhaps without peg/RBV. Of note, Roche announced last week they are planning to begin soon the first stud of a combination of 2 oral drugs, since they are developing 2 oral drugs ITM191, a potent protease inhibitor which is currently being studied in patients, and R7128 the Pharmasset/Roche potent polymerase inhibitor. Conducting this study will establish the effectiveness of 2 oral drug combinations and should a major advancent in realizing the benefits of using  oral drugs in regards to supressing the develoment of drug resistance. Because using 2 oral drugs should show a capacity to delay and avoid drug resistance. At the conference the new BMS NS5A inhibitor, the first in this new class of drugs received quite a lot of attention because although only 1 dose was given in this first study in patients it achieved a potent 3.6 log reduction and patients stayed undetectable for 144 hours. Merck presented for the first time study results of their HCV protease inhibitor which was also very impressive. Tibotec presented new studies with an adjusted dosing regimen which also showed potency and promise for moving ahead with further studies. Pfizer presented for the first time study results for their new HCV polymerase inhibitor and this drug also looks potent and promisin. Idenix has several new HCV drugs in development and although these reports are not listed below this week I will finish these reports; unfortunately there were 4 HIV and hepatitis conferences all back to back so I am working extra hard to get all these conferences reports out. Anadys reported new study results although very ealy fo their new HC drug. Just prior to the conference GSK announced they purchased the HCV drug development program from Genelabs whi are developing HCV NRTIs. Of interest some NNRTIs can be perhaps combined in the same regimen because they can bind at different sites. And thee are additional HCV drugs in development by Abbott and other companies. So the prospect for combining multiple oral drugs in effective 2 and 3 drug regimens are expected. We can I think expect potent combinations where the goal of researchers is to achieve a very potent reduction in viral load and high cure rates. I think in the future we will be able to achieve 80-90% cure rates for all.59th Annual Meeting of the American Association for the Study of Liver Diseases Oct 31-Nov 1 2008San Francisco, CA59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)Oct 31-Nov 1 2008San Francisco, CA  Metformin with Peginterferon Alfa-2a and Ribavirin in the Treatment of Naive Genotype 1 Chronic Hepatitis C Patients with Insulin Resistance (TRIC-1): Final Results of a Randomized and Double-Blinded Trial - (11/21/08) SVR in African American Patients: Results of the IDEAL Study (Individualized Dosing Efficacy vs Flat Dosing to Assess OptimaL Pegylated Interferon Therapy)- (11/21/08) A Study of Telaprevir Combined with Peginterferon Alfa-2a and Ribavirin in Patients with Well-documented Non-response or Relapse After Previous Peginterferon Alfa-2a and Ribavirin Treatment: Interim Analysis - (11/20/08)Safety and antiviral activity of BI 201335, a new HCV NS3 protease inhibitor, in combination therapy with peginterferon alfa-2a (P) and ribavirin ® for 28 days in P+R treatment-experienced patients with chronic hepatitis C genotype 1 infection - (11/14/08) Safety, Tolerability, and Pharmacokinetic Data Following Single- and Multiple-Dose Administration of MK-7009, a Hepatitis C Virus Non-structural 3/4a Protease Inhibitor, to Healthy Male Subjects (1910) - (11/14/08)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 - (11/12/08) Safety, Tolerability, and Pharmacokinetic Data Following Single- and Multiple-Dose Administration of MK-7009, a Hepatitis C Virus Non-structural 3/4a Protease Inhibitor, to Healthy Male Subjects (1910) - (11/11/08) Pharmacokinetics of once-daily regimens of the novel HCV NS3/4A-protease inhibitor TMC435350, with and without peg-IFN and ribavirin, in HCV-infected individuals - (11/11/08) Inhibitory activity of TMC435350 on HCV NS3/4A proteases from genotypes 1 to 6 - (11/11/08) 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 - (11/07/08) New HCV Drugs at AASLD: Vertex is Focus at Hepatitis C Meeting - (11/07/08) 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 - (11/07/08) Anadys Pharmaceuticals Announces Single Dose Safety and Pharmacokinetics Results for ANA598 in Healthy Volunteers Phase I Clinical Data and Additional Preclinical Results for Non-Nucleoside HCV Polymerase Inhibitor Being Presented at AASLD - (11/07/08) Antiviral Activity of the HCV Polymerase Inhibitor PF-00868554 Administered as Monotherapy in HCV Genotype 1 Infected Subjects - (11/07/08)Telaprevir in Combination with Peginterferon-a-2a With or Without Ribavirin in the Treatment of Chronic Hepatitis C Treatment-Naïve Genotype 1: Final Results of the PROVE2 Study (conducted in Europe) - (11/06/08) A Phase 2b Study of Telaprevir with Peginterferon-Alfa-2a and Ribavirin in Hepatitis C Genotype 1 Null and Partial Responders and Relapsers Following a Prior Course of Peginterferon-Alfa-2a/b and Ribavirin Therapy: PROVE3 Interim Results - (11/06/08) Safety and antiviral activity of BI 201335, a new HCV NS3 protease inhibitor, in treatment-naive patients with chronic hepatitis C genotype 1 infection given as monotherapy and in combination with peginterferon alfa-2a (P) and ribavirin ®- (11/06/08) Treatment of Chronic Hepatitis C Virus (HCV) Genotype 1 Patients with the NS3/4A Protease Inhibitor ITMN-191 Leads to Rapid Reductions in Plasma HCV RNA: Results of a Phase 1b Multiple Ascending Dose (MAD) Study - (11/05/08) Intravenous silibinin for treatment of nonresponders to peginterferon/ribavirin therapy in chronic hepatitis C - (11/05/08) Safety and antiviral activity of TMC435350 in treatment-naive genotype 1 HCV-infected patients - (11/04/08) Safety, Tolerability and Antiviral Activity of MK-7009, a Novel Inhibitor of the Hepatitis C Virus NS3/4A Protease, in Patients with Chronic HCV Genotype 1 Infection - (11/04/08) GlobeImmune Hepatitis C Therapeutic Vaccine, GI-5005, Doubles Viral Clearance And Increases RVR Rates In Phase 2 Clinical Trial - (11/04/08) Boceprevir Plus Peginterferon alfa-2b/Ribavirin for Treatment of Genotype 1 Chronic Hepatitis C in Previously Untreated Patients: Interim Results from the HCV SPRINT-1 Study - (11/04/08) BMS-790052 is a First-in-class Potent Hepatitis C Virus (HCV) NS5A Inhibitor for Patients with Chronic HCV Infection: Results from a Proof-of-concept Study - (11/04/08) An On-going Outbreak of Acute HCV in HIV-infected Men in New York City: Rates of Spontaneous Clearance, Treatment Responses, and Liver Fibrosis - (11/3/08) New Clinical Data Support Broad Profile for Telaprevir in Patients with Genotype 1 Hepatitis C Virus (HCV) Infection - (11/3/08) Boceprevir Phase II Study Showed High Rate of Sustained Response With 28- and 48-Week Regimens in Genotype 1 Treatment-Naive Hepatitis C Patients - (11/3/08) TIBOTEC PRESENTS INTERIM FINDINGS FOR TMC435, AN INVESTIGATIONAL GENOTYPE 1 HEPATITIS C TREATMENT, AT THE AASLD LIVER MEETING 2008 - (11/3/08)