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New HCV Drugs new nukes-NS5A/Protease Inhibitors
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Reported by Jules Levin
Here is a link to the 100+ reports I filed of studies at EASL........
EASL - The International Liver Congress 2015 50th Annual Meeting of the European
Association for the Study of the Liver Vienna, Austria April 22-26
The key stories & themes include the large global phase 3 study results from Merck as the FDA is expected to approve the Merck regimen by November 2015; numerous daclatasvir studies were reported including their large phase 3 studies ALLY1/2/3 and clinical experiences from compassionate use programs & cohorts in Europe, and the FDA is expected to approve daclatasvir by August 2015; their were a bunch of studies with successful post liver transplant treatment and successful therapy in renal impaired patients. There were a lot of studies reporting how SVR improves long-term health & cost-effectiveness studies. There were a bunch of studies reporting the prevalence & effects of resistance regarding the HCV drugs. There was an interesting study finding what we expected, that HCV increased cancer rates, that is non-HCV cancers, but we expected that. There were a few studies showing earlier HCV treatment is better than delaying treatment, it improves outcomes & is cost saving. There was a study on Global Hepatitis Burden reporting: "Between 1990---2013, deaths due to HCV more than doubled.....liver cancer deaths due to HCV increased 300%.....deaths due to HBV increased by one third [http://www.natap.org/2015/EASL/EASL_46.htm]"
New Nukes, and new/2nd Gen NS5A & Protease Drugs
Reported by Jules Levin
EASL: HIGH EFFICACY OF RETREATMENT WITH LEDPASVIR AND SOFOSBUVIR IN HCV PATIENTS WHO FAILED INITIAL SHORT COURSE THERAPY WITH COMBINATION DAA REGIMENS (NIH SYNERGY TRIAL) - (04/28/15)
Regarding persistence of mutations/resistance, this study reported NS3/protease mutations declined & were detectable in only 4% of patients after 168 days following failed treatment but NS5A mutations persisted.....
EASL: LONG-TERM FOLLOW-UP OF TREATMENT-EMERGENT RESISTANCE-ASSOCIATED VARIANTS IN NS3, NS5A AND NS5B WITH PARITAPREVIR/r-, OMBITASVIR- AND DASABUVIR-BASED REGIMENS - (04/24/15)
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New Nukes......new nukes (like sofosbuvir) from Merck, Achillion, J&J, Medivir
EASL: PRECLINICAL CHARACTERISATION OF MIV-802, A NOVEL URIDINE NUCLEOTIDE HCV NS5B POLYMERASE INHIBITOR, FOR TREATMENT OF HEPATITIS C VIRUS INFECTION - (05/18/15)
EASL: Merck HCV Nuk MK3682 7-Day Monotherapy - (05/05/15)
EASL: Preclinical Characterization of AL-335 (J&J), a Potent Uridine Based Nucleoside Polymerase Inhibitor for the Treatment of Chronic Hepatitis C - (05/05/15)
EASL: Derisking the Potential for Mitochondrial Toxicity of Nucleoside Analogs - (05/05/15)
EASL: ACH-3422, a Novel Nucleotide Prodrug Inhibitor of HCV NS5B Polymerase - monotherapy study in patients- (04/31/15)
EASL: ACHIEVEMENT OF SVR24 DESPITE THE PRESENCE OF HCV VARIANTS RESISTANT TO FIRST-GENERATION NS5A INHIBITORS IN GENOTYPE-1 HEPATITIS C PATIENTS AFTER 8-WEEK THERAPY OF ACH-3102 IN COMBINATION WITH SOFOSBUVIR - (04/31/15)
PRECLINICAL CHARACTERISTICS OF ACH-3422: A POTENT URIDINE NUCLEOTIDE PRODRUG FOR INHIBITION OF HEPATITIS C VIRUS NS5B RNA POLYMERASE......http://www.natap.org/2013/AASLD/AASLD_64.htm
EASL: Sustained Virologic Response After ACH-3102 and Sofosbuvir Treatment for 8 or 6 Weeks: a Phase 2 "Proxy" Study - (04/31/15)
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New NS5A, Protease Inhibitors......if you click on the links to the early/preclinical studies of these drugs you will see their potency against NS5A & protease mutations/resistance. new 2nd generation NS5A inhibitors from Gilead (GS5816), Abbvie (ABT530), Merck (MK8408), Achillion (ACH3102) and new 2nd generation protease inhibitors from Gilead (GS9857), Abbvie (ABT493), Merck's MK5172 is also a more potent advanced PI; it appears from several recent studies that protease mutations may disappear largely thereby not necessarily sidelining earlier protease inhibitors, but NS5A mutations persist and will be a concern; and at the bottom below a new HCV drug in a new class, a monthly injectable possibly miR122 inhibitor.
EASL: Evaluation of the Pangenotypic HCV NS3/4A Protease Inhibitor GS-9857 in Healthy Volunteers - (04/29/15)
EASL: Preclinical Profile of the Pangenotypic HCV NS3/4A Protease Inhibitor GS-9857 - (04/29/15)
EASL: Safety and Efficacy of Short-Duration Treatment With GS-9857 Combined With Sofosbuvir/GS-5816 in Treatment-Naļve and DAA-Experienced Genotype 1 Patients With and Without Cirrhosis - (04/24/15)
EASL: Resistance Analysis of Treatment-Experienced Genotype 1 and 3 HCV-Infected Patients Treated With Sofosbuvir in Combination With GS-5816 ± Ribavirin for 12 Weeks - (05/04/15)
EASL: The ASTRAL Studies: Evaluation of SOF/GS-5816 Single-Tablet Regimen for the Treatment of Genotype 1-6 HCV Infection - (05/04/15)
A Next Generation HCV DAA Combination: Potent, Pangenotypic Inhibitors ABT-493 and ABT-530 With High Barriers to Resistance.....http://www.natap.org/2014/AASLD/AASLD_51.htm
EASL: 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 - (05/04/15)
EASL: Steady-State Pharmacokinetics and Safety of Co-administration of Pan-Genotypic Direct Acting Protease Inhibitor ABT-493 with Pan-Genotypic NS5A Inhibitor ABT-530 in Healthy Adult Subjects - (05/04/15)
EASL: Pharmacokinetics of ABT-493 and ABT-530 is Similar in Healthy Caucasian, Han Chinese, and Japanese Adult Subjects - (05/04/15)
EASL: No Significant Interaction Among Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir and Sofosbuvir - (04/27/15)
EASL: A Phase 1 Study to Evaluate the Interaction of HCV NS5B Inhibitor MK-3682 With HCV NS3/4A Protease Inhibitor MK-5172 and HCV NS5A Inhibitor MK-8408 in Healthy Subjects - (04/23/15)
MK-8408, a Potent and Selective NS5A Inhibitor With a High Genetic Barrier to Resistance and Activity Against HCV Genotypes 1-6......http://www.natap.org/2014/AASLD/AASLD_40.htm
The Combination of Grazoprevir (MK-5172), an NS3 Inhibitor, and MK-8408, an NS5A Inhibitor, Presents a High Genetic Barrier to Resistance in HCV Genotypes 1a and 3a.......http://www.natap.org/2014/AASLD/AASLD_56.htm
EASL: Resistance Analysis of Virologic Failures in Hepatitis C Genotype 1-Infected Patients Treated With Grazoprevir + Elbasvir ± Ribavirin: the C-WORTHY Study - (05/04/15)
FINDINGS FROM CLINICAL VIROLOGY STUDIES ON ACH-3102 ARE CONSISTENT WITH PRECLINICAL OBSERVATIONS ON ITS IMPROVED POTENCY AGAINST GENOTYPE-1A HCV AND RESISTANT VARIANTS.......http://www.natap.org/2013/EASL/EASL_84.htm
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......http://www.natap.org/2013/EASL/EASL_85.htm
EASL/2012: PRECLINICAL CHARACTERISTICS OF ACH-3102: A NOVEL HCV NS5A INHIBITOR WITH IMPROVED POTENCY AGAINST GENOTYPE-1A VIRUS AND VARIANTS RESISTANT TO 1ST GENERATION NS5A INHIBITORS.....http://www.natap.org/2012/EASL/EASL_79.htm
EASL/2013: ACH-3102, A Second Generation NS5A Inhibitor, Demonstrates Potent Antiviral Activity (single-dose) in Patients with Genotype 1A HCV Infection Despite the Presence of Baseline NS5A-Resistant Variants ........http://www.natap.org/2013/EASL/EASL_85.htm
EASL/2013: FINDINGS FROM CLINICAL VIROLOGY STUDIES ON ACH-3102 ARE CONSISTENT WITH PRECLINICAL OBSERVATIONS ON ITS IMPROVED POTENCY AGAINST GENOTYPE-1A HCV AND RESISTANT VARIANTS......http://www.natap.org/2013/EASL/EASL_84.htm
ACH-3102 and Ribavirin in Genotype-1b Hepatitis C Patients: Confirmation of the High Barrier to Viral Breakthrough in Genotype-1b HCV......http://www.natap.org/2014/APASL/APASL_28.htm
EASL: A Single Subcutaneous Dose of 2 mg/kg or 4 mg/kg of RG-101, a Galnac-Conjugated Oligonucleotide with Antagonist Activity against miR-122, Results in Significant Viral Load Reductions in Chronic Hepatitis C Patients - (04/27/15)
EASL: Pharmacokinetics of Miravirsen, a miR-122 Inhibitor, Predict the Prolonged Viral Load Reduction in Treatment Naive Genotype 1 HCV-Infected Patients - (04/27/15)
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