New HCV Drugs at AASLD

62th Annual Meeting of the American
Association for the Study of Liver Diseases
San Francisco 2011 Nov 6-9

from Jules of NATAP: There were so many positive presentations on new HCV drugs in development that one can only conclude SVR/'cure rates' will eventually be 100% for all treatable patients, whether patients are white, black or gentotypes 1 or 2/3. The once-daily HCV nucleotide PSI-7977 captured the imagination at AASLD with studies in only 40 patients with genotype 2/3 showing 100% cure rates receiving interferon-free regimen of PSI-7977+ribavirin for only 12 weeks, in this study their are 4 different regimens studied, see the link below to read the entire details. In the genotype 1 study 95 patients received PSI-7977+peg/rbv for 12 weeks followed by 12 additional weeks of Peg/Rbv alone, with 91-98% SVR rates, there were no viral failures, 4 patients withdrew due to Peg/Rbv side effects. This drug is entering Phase 3 studies in the Spring 2012, the last phase before FDA approval, which could take until 2014. The manufacturer Pharmasset has a 2nd nucleotide PSI-938 in earlier development and has already conducted studies combining these 2, and will conduct further studies combining them. Two other major classes of drugs are in accelerated development. The potent once-daily BMS NS5A inhibitor BMS-790052 is moving quickly through development being studied currently in an interferon-free 2-drug combination in genotype 1 patients with PSI-7977, the study is ongoing and results are not ready yet. Several studies of BMS-790052 presented at AASLD are reported below. Currently in Phase 3 are 2 new HCV protease inhibitors Tibotec's once-daily TMC-435 and Boerhinger Ingelheim's once-daily BI-201355, both are potent, and study results for both drugs were presented at AASLD and are linked to below. Tibotec is also studying their protease TMC-435 in combination with PSI-7977. BI also reported study results at AASLD of their interferon-free regimen which includes their protease BI-201335 + their NNRTI BI-207127 and ribavirin, linked to below. Tibotec announced study results for the first time for a new NNRTI TMC-647055, results presented below. Roche reported study results for their potent HCV protease danoprevir, linked to below, and will present at EASL new results of low-dose ritonavir boosted danoprevir in the near future. Study results of a combination of the BMS NS5A + their HCV protease BMS-790032 was reported at AASLD, linked to below. The first-in-class cyclophillin inhibitor from Novartis potent alisporivir/DEB025 is currently in phase 3 development, study results in genotype 1 were reported last Spring at EASL and study results in genotype 2 were reported at AASLD, linked to below. Vertex reported study results of their potent QUAD therapy regimen which includes telaprevir+ their NNRTI VX-222 + Peg/Rbv, results reported below. Merck reported early study results from an 8-day monotherapy study of their potent 2nd generation HCV protease inhibitor MK-5172, which showed 5 to 5.5 log reductions, so far perhaps the most potent protease, and they presented a poster showing in vitro this protease is active against, it suppresses protease resistant viruses, suggesting patients who fail with resistance would benefit from this protease and it would also be a potent first-line protease for treatment-naive patients, these studies linked to below. Merck also reported their first study pre-clinical data for a new NS5A inhibitor MK-4882 they discovered & are developing, which appears potent showing 4-log viral load reductions in the chimp after, linked to below. GSK reported for the first time on their new potent NS5A inhibitor GSK-2336805 showing early results from a single and repeat dose study in patients, see link below to view results. Gilead is researching 2, 3 and 4 drug HCV regimens with and without interferon and without ribavirin, Gilead has drugs of their own in every class including protease, NNRTI, NS5A and nucleotide, and have studies exploring these regimens ongoing, with further results to be presented in the near future, they did present some preliminary study data at AASLD, linked to below, but the study results expected to be reported in the near future from these ongoing studies will be much more informative and are highly anticipated. Abbott as well is in the middle of conducting ongoing studies so they did not have any study results to report at AASLD, but they have a potent HCV protease, 2 NNRTIs, and other classes of drugs in development, so it is expected they will in the near future also be presenting highly anticipated results from these ongoing studies. Presidio, a small biotech, is developing a potent NS5A inhibitor PPI-461and reported results from their dose-ranging study at AASLD, linked to below. Achillion & Inhibitex, 2 small biotechs, reported very promising study data on their drugs, Achillion is developing a potent HCV protease and a promising 2nd generation NS5A inhibitor, expected to be active against, to suppress NS5A resistant virus, they reported interesting data at AASLD, linked to below. As well Inhibitex reported their first new data on a higher dose of their nucleotide INX-189 at AASLD, it looks potent, data linked to below. BMS reported study results for their new peg-lambda interferon showing it to be potent with much less side effects, linked to below. Roche is developing a nuke mericitabine, it is rather advanced stage of development, and they reported encouraging resistance data, linked to below. In sum, is there any doubt that we can eventually expect a 100% 'cure rate' in all patients who will be treatable.

AASLD: PROTON: PSI-7977 & Peg/RBV in Treatment-naïve Patients with HCV GT1: Sustained Virologic Response - (11/08/11)

AASLD: PSI-7977: ELECTRON Interferon is not required for Sustained Virologic Response in Treatment-Naïve Patients with HCV GT2 or GT3 - (11/07/11)

AASLD: High sustained virologic response (SVR24) rates with response-guided danoprevir (DNV; RG7227) plus PegIFN alfa-2a (40KD) and ribavirin (P/R) in treatment-naive HCV genotype 1 (G1) patients: results from the ATLAS study - (11/07/11)

AASLD: Treatment with the 2nd generation HCV protease inhibitor BI 201335 results in high and consistent SVR rates - results from SILEN-C1 in treatment-naïve patients across different baseline factors - (11/08/11)

AASLD: High SVR following IFN-free treatment of chronic HCV GT1 infection for 4 weeks with HCV protease inhibitor BI 201335, polymerase inhibitor BI 207127 and ribavirin, followed by BI 201335 and PegIFN/ribavirin - the SOUND-C1 study - (11/08/11)

AASLD: Virologic response to an interferon-free regimen of BI 201335 and BI 207127, with and without ribavirin, in treatment-naïve patients with chronic genotype-1 HCV infection: Week 12 interim results of the SOUND-C2 study - (11/08/11)

AASLD: SILEN-C3: treatment for 12 or 24 weeks with BI 201335 combined with peginterferon alfa-2a and ribavirin in treatment-naïve patients with chronic genotype-1 HCV infection - (11/07/11)

AASLD: Positive Interim Results from Interferon-Free Phase 2b SOUND-C2 Study with Boehringer Ingelheim's Two Investigational HCV Direct Acting Antivirals Presented at AASLD - press release - (11/08/11)

AASLD: Once-daily alisporivir interferon (IFN)-free regimens achieve high rates of early HCV clearance in previously untreated patients with HCV genotype (G) 2 or 3 - (11/09/11)

AASLD: Novartis DEB025 data showed viral clearance as early as six weeks and potential for interferon-free therapy in hepatitis C patients - (11/07/11)

AASLD: TMC435 in Combination with Peginterferon and Ribavirin in Treatment-naïve HCV Genotype 1 Patients: Final Analysis of the PILLAR Phase IIb Study (TMC435-C205) - (11/08/11)

AASLD: Human safety, pharmacokinetics and antiviral activity of TMC647055, a novel HCV non-nucleoside polymerase inhibitor - (11/07/11)

AASLD: QUAD VX-222/Telaprevir in Combination With Peginterferon-alfa-2a and Ribavirin in Treatment-naïve Genotype 1 HCV Patients Treated for 12 Weeks: ZENITH Study, SVR12 Interim Analysis - (11/09/11)

AASLD: Daclatasvir (DCV; BMS-790052), an NS5A Replication Complex Inhibitor, in Combination With Peginterferon Alfa-2b and Ribavirin in Japanese Treatment-Naïve and Nonresponder Patients With Chronic HCV Genotype 1 Infection - (11/10/11)

AASLD: Combination Therapy of Treatment-Naïve and Nonresponder Patients With HCV Genotype 1 Infection With Daclatasvir (DCV; BMS-790052), an NS5A Replication Complex Inhibitor, in Combination With Peginterferon Alfa-2a and Ribavirin - (11/10/1

AASLD: Dual Oral Combination Therapy with the NS5A Inhibitor Daclatasvir(DCV; BMS-790052) and the NS3 Protease Inhibitor Asunaprevir(ASV; BMS-650032) Achieved 90% Sustained Virologic Response (SVR12) in Japanese HCV Genotype 1b-Infected Null Responders - (11/08/11)

AASLD: Evaluation of Drug Interaction Potential of the HCV Protease Inhibitor Asunaprevir (ASV; BMS-650032) at 200 mg Twice Daily (BID) in Metabolic Cocktail and P-glycoprotein (P-gp) Probe Studies in Healthy Volunteers - (11/16/11)

AASLD: Single-Dose Pharmacokinetics of Daclatasvir (DCV; BMS-790052) in Subjects With Hepatic Impairment Compared With Healthy Subjects - (11/16/11)

AASLD: Daclatasvir (DCV; BMS-790052) Has No Clinically Significant Effect on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate in Healthy Female Subjects - (11/16/11)

AASLD: GSK2336805 HCV NS5A Inhibitor Demonstrates Potent Antiviral Activity in Chronic Hepatitis C (CHC) Genotype 1 Infection: Results from a First Time in Human (FTIH) Single and Repeat Dose Study - (11/09/11)

AASLD: Dose-Ranging Trial of PPI-461, a Potent New Pan-Genotypic HCV NS5A Inhibitor, in Patients with HCV Genotype-1 Infection - (11/07/11)

AASLD: Antiviral Activity/Resistance Monitoring of HCV Patients Treated for Three Days with the NS5A Inhibitor PPI-461 Reveals Rapid Emergence of Resistant HCV Variants - (11/07/11)

Inhibitex Nucelotide INX-189 Higher Dosing Increases Viral Load Reduction - Inhibitex reports third quarter financial results and recent corporate developments - (11/07/11)

AASLD: Antiviral Activity and Safety of INX-08189, a Nucleotide Polymerase Inhibitor, Following 7-Days of Oral Therapy in Naïve Genotype-1 HCV Patients - (11/07/11)

AASLD: Safety and Efficacy of Peginterferon Lambda-1a (Lambda) Compared With Peginterferon Alfa-2a (Alfa-2a) in HCV-Infected Patients (G1/2/3) With Compensated Cirrhosis: EMERGE Phase 2B Efficacy and Safety Results Through Week 12 - (11/10/11)

AASLD: NO DETECTION OF VARIANTS BEARING NS5B S282T MERICITABINE (MCB) RESISTANCE MUTATION IN DAA TREATMENT-NAIVE HCV GENOTYPE 1-INFECTED PATIENTS USING ULTRA-DEEP PYROSEQUENCING (UDPS) - (11/16/11)

AASLD: Safety and Antiviral Activity of MK-5172, a Next Generation HCV NS3/4a Protease Inhibitor with a Broad HCV Genotypic Activity Spectrum and Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients - (11/07/11)

AASLD: MK-5172, a Second Generation HCV NS3/4A Protease Inhibitor is Active Against Common Resistance Associated Variants (RAVs) and Exhibits Cross-Genotype Activity - (11/07/11)

AASLD: Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Relationship for MK-5172, a Novel Hepatitis C Virus (HCV) NS3/4A Protease Inhibitor, in Genotype 1 and Genotype 3 HCV-Infected Patients - (11/16/11)

AASLD: Discovery of MK-4882, a Novel Inhibitor of HCV NS5a with an Attractive Pre-clinical Profile - (11/07/11)

AASLD: The Effects of Combining Two Gilead Direct Acting Antivirals GS-9256+GS-9190, Ribavirin, and Pegylated Interferon on the Detection of Drug Resistance Mutations Early in Treatment of HCV - (11/15/11)

AASLD: Evaluation of Pre-Existing Levels of Y448H HCV NS5B Polymerase Mutant Using Viral Kinetics Monitored by Allele-Specific PCR in HCV Patients and Replicon Cells Treated with the HCV Non-Nucleoside Inhibitor Tegobuvir - (11/15/11)

AASLD: Characterization of HCV Resistance from a Multiple Dose Clinical Trial of GS-5885, a Novel HCV NS5A Inhibitor - (11/15/11)

AASLD: In Vitro Selection of Resistance to GS-9451, a Novel and Potent Inhibitor of HCV NS3 Protease - (11/15/11)

AASLD: HIGH RAPID VIROLOGIC RESPONSE (RVR) WITH ACH-1625 DAILY DOSING PLUS PEGIFN- ALPHA 2A/RBV IN A 28-DAY PHASE 2A TRIAL - (11/10/11)

AASLD: PHARMACOKINETIC MODELING OF ACH-2684, A HEPATOSELECTIVE PHASE I PAN-GENOTYPIC HCV NS3 PROTEASE INHIBITOR: PREDICTIONS AND CORRELATION WITH HUMAN PHARMACOKINETICS - (11/10/11)

AASLD: Novel Hepatitis C Virus NS5A Inhibitors with Improved Potency Against Genotype-1a Replicons and Replicons Carrying Mutations Associated With Viral Resistance to 1st Generation NS5A Inhibitors - (11/10/11)

AASLD: Once-Daily Narlaprevir (NVR; SCH 900518) and Ritonavir (RTV) in Combination With Peginterferon Alfa-2b/Ribavirin (PR) for 12 Weeks Plus 12 Weeks PR in Treatment-Naive Patients With HCV Genotype 1 (G1): SVR Results From NEXT-1, a Phase 2 Study - (11/16/11)

AASLD: Safety and Efficacy of Vaniprevir (MK-7009) in Combination with Peg-interferon a-2a (Peg-IFN)/Ribavirin (RBV) in Genotype 1 Treatment-Experienced HCV-Infected Japanese Patients - (11/16/11)

AASLD: A Phase 2b Study of MK-7009 (vaniprevir) in Patients with Genotype 1 HCV Infection Who HaveFailed Previous Pegylated Interferon and Ribavirin Treatment - (11/15/11)

HBV AASLD

AASLD: Baseline and early on-treatment characteristics in HBeAg-positive patients with chronic hepatitis B infection achieving an early on-treatment response to pegylated interferon alfa-2a (40KD): interim results from the RGT study - (11/20/11)

AASLD: Patients with HBeAg-positive chronic hepatitis B with a maintained virologic response to entecavirachieved HBsAg clearance when switched to peginterferon alfa-2a (40KD) therapy (the OSST study) - (11/16/11)

AASLD: A novel combination regimen of peginterferon alfa-2a (40KD) and entecavir results in sustained post-treatment HBsAg clearance in HBeAg-positive chronic hepatitis B - (11/16/11)

AASLD: Peginterferon alfa-2a monotherapy as a strategy for achieving sustained response in patientsswitched from long-term nucleos(t)ide analog therapy: the results of 1 year follow up - (11/16/11)

AASLD: A response-guided approach to pegylated interferon alpha-2a (40KD) therapyto improve response rates in HBeAg-negative, genotype D patients - (11/16/11)

AASLD: Response rates are similar for patients with and without advanced fibrosis/cirrhosis, and highest with peginterferon alfa-2a (40KD) 180 μg for 48 weeks in the NEPTUNE study - (11/16/11)

AASLD: Five years of Treatment with Tenofovir DF for Chronic Hepatitis B Infection is Associated with Sustained Viral Suppression and Significant Regression of Histological Fibrosis and Cirrhosis - (11/14/11)

AASLD: No Detectable Resistance to Tenofovir Disoproxil Fumarate (TDF) Following up to 240 Weeks of Treatment in Patients with HBeAg+ and HBeAg-Chronic Hepatitis B Virus Infection - (11/14/11)

AASLD: Five years of Treatment with Tenofovir DF for Chronic Hepatitis B Infection in Asian Patients is Associated with Sustained Viral Suppression and Significant Regression of Histological Fibrosis and Cirrhosis - (11/14/11)

AASLD: Gilead Announces Positive Five-Year Data Showing Effect of Viread(R) on Liver Fibrosis and Cirrhosis Caused by Chronic Hepatitis B: '88% of patients on tenofovir in studies experienced reversal of fibrosis/cirrhosis' - press release - (11/14/11)

AASLD: Entecavir (ETV) monotherapy for 96 weeks is comparable to combination therapy with ETV plus tenofovir (TDF) in nucleos(t)ide-naïve patients with chronic hepatitis B (CHB): the BE-LOW study - (11/10/11)

AASLD: Phase IIIb Comparison of BARACLUDE® (entecavir) Monotherapy Versus BARACLUDE Plus Tenofovir Combination Shows No Statistical Difference Between Study Arms - press release - (11/10/11)