Hepatitis C New D...
Follow
Find
15.9K views | +5 today
Hepatitis C New Drugs Review
FDA approved Incivek(telaprevir, Vertex) on Monday 23 May by its PDUFA deadline.A paradigm shift in the treatment of Hepatitis C virus infection. http://knol.google.com/k/krishan-maggon/boceprevir-merck-telaprevir-vertex/3fy5eowy8suq3/151#
Curated by Krishan Maggon
Your new post is loading...
Your new post is loading...
Scooped by Krishan Maggon
Scoop.it!

Management of acute and chronic HCV infection in persons with HIV coinfection - Journal of Hepatology

Management of acute and chronic HCV infection in persons with HIV coinfection - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it
Summary

Due to shared routes of transmission, acute and chronic infection with hepatitis C virus is common among persons living with HIV infection in many regions of the world. In the era of effective antiretroviral therapy, acute HCV infection has been increasingly recognized in HIV-infected persons, particularly men who have sex with men, and liver disease, including hepatocellular carcinoma, has emerged as a leading cause of morbidity and mortality in those with chronic HCV infection, particularly older adults with long-standing coinfection. Over the past decade, the foundation for the management of acute and chronic HCV infection has been interferon alfa. However, due the high burden of treatment-related side effects and low likelihood of sustained virologic response, the impact of treatment with peginterferon/ribavirin on the burden of HCV disease in has been limited. However, the anticipated availability of safe, tolerable and highly efficacious interferon-free, oral HCV direct-acting antiviral combination therapies promise to dramatically change the management of acute and chronic HCV infection in HIV-infected persons. Preliminary data from studies of such oral DAA regimens in HIV/HCV coinfected patients suggest that coinfection with HIV will not impair HCV cure with these regimens. Indeed, in the coming era of high effective oral HCV DAA treatments, the only special feature concerning treatment of acute and chronic HCV infection in HIV-infected patients may be drug interactions between the antiretroviral drugs for HIV infection and direct-acting antiviral drugs for HCV infection.

Krishan Maggon 's insight:

J. Hepatology

 

November 2014Volume 61, Issue 1, Supplement, Pages S108–S119Management of acute and chronic HCV infection in persons with HIV coinfectionMark S. SulkowskiJohns Hopkins University, School of Medicine, Baltimore, MD, United StatesOpen AccessDOI: http://dx.doi.org/10.1016/j.jhep.2014.08.006
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

HCV animal models and liver disease - Journal of Hepatology

HCV animal models and liver disease - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it
Summary

The development and evaluation of effective therapies and vaccines for the hepatitis C virus (HCV) and the study of its interactions with the mammalian host have been hindered for a long time by the absence of suitable small animal models. Due to the narrow host tropism of HCV, the development of mice that can be robustly engrafted with human hepatocytes was a major breakthrough since they recapitulate the complete HCV life cycle. This model has been useful to investigate many aspects of the HCV life cycle, including antiviral interventions. However, studies of cellular immunity, immunopathogenesis and resulting liver diseases have been hampered by the lack of a small animal model with a functional immune system. In this review, we summarize the evolution of in vivo models for the study of HCV.

Krishan Maggon 's insight:

J. Hepatology

 

November 2014Volume 61, Issue 1, Supplement, Pages S26–S33

HCV animal models and liver diseaseKoen Vercauteren, Ype P. de Jong, Philip MeulemanOpen AccessDOI: http://dx.doi.org/10.1016/j.jhep.2014.07.013
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases - Journal of Hepatology

Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseases - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it
Summary

The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. A significant portion of the morbidity and mortality associated with HCV is a consequence of numerous HCV-associated comorbidities. Type 2 diabetes and atherosclerosis, two known complications of the metabolic syndrome, are noteworthy, because HCV has been suggested to play a role in their pathogenesis. In addition, HCV also causes steatosis, which may increase the risk of cardiovascular events. This review summarizes the evidence supporting the association between HCV and steatosis, insulin resistance/type 2 diabetes and cardiovascular morbidity and mortality. Their diagnostic, prognostic and management aspects are discussed.

Krishan Maggon 's insight:

J. Hepatology                                                                          November 2014Volume 61, Issue 1, Supplement, Pages S69–S78

 

 

Facts and fictions of HCV and comorbidities: Steatosis, diabetes mellitus, and cardiovascular diseasesFrancesco NegroDivisions of Gastroenterology and Hepatology, University Hospitals, Geneva, SwitzerlandDivision of Clinical Pathology, University Hospitals, Geneva, SwitzerlandOpen AccessDOI: http://dx.doi.org/10.1016/j.jhep.2014.08.003
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Regulus Therapeutics RG-101 Potent, Durable and Pan-Genotypic Effects in Diverse HCV Population. Late-Breaking ILC 2015

Regulus Therapeutics RG-101 Potent, Durable and Pan-Genotypic Effects in Diverse HCV Population. Late-Breaking ILC 2015 | Hepatitis C New Drugs Review | Scoop.it
Late-Breaking Oral Presentation at The International Liver Congressb" (ILC ...

 

LA JOLLA, Calif., April 25, 2015 /PRNewswire/ -- Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today presented new data strengthening the profile of RG-101, a wholly-owned, GalNAc-conjugated anti-miR targeting microRNA-122 ("miR-122") for the treatment of HCV, during an oral late-breaking session at ILC 2015 in Vienna, Austria. Extended follow-up results evaluating a single subcutaneous administration of either 2 mg/kg or 4 mg/kg of RG-101 as monotherapy in HCV patients with varied genotypes, liver fibrosis status and treatment history showed that 10/22 patients had HCV RNA levels below the limit of quantification ("BLOQ") at 12 weeks and 70 percent of those patients remained BLOQ at 20 weeks (7/10).  In addition, the positive results that were previously reported from the completed clinical study of RG-101 were reviewed during the oral late-breaker.

Krishan Maggon 's insight:

Targeting microRNAs with anti-miRs, chemically modified, single-stranded oligonucleotides, offers a unique approach to treating disease by modulating entire biological pathways and may become a new and major class of drugs with broad therapeutic application.


RG-101 is a  GalNAc-conjugated anti-miR targeting microRNA-122 ("miR-122") for the treatment of HCV. 

 

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Merck Grazoprevir/Elbasvir Phase 2 Clinical Results Hepatitis C Therapy at the International Liver Congress 2015

Merck Grazoprevir/Elbasvir Phase 2 Clinical Results Hepatitis C Therapy at the International Liver Congress 2015 | Hepatitis C New Drugs Review | Scoop.it

VIENNA – April 25, 2015 – Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from two Phase 2 clinical trials evaluating the safety and efficacy of the company’s investigational once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg)[1] in adult patients with chronic hepatitis C virus (HCV) infection. Treatment with grazoprevir and elbasvir in combination with ribavirin (RBV) (C-SALVAGE trial) showed high rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) in patients with chronic HCV genotype 1 (GT1) infection with or without liver cirrhosis who previously failed combination therapy with a DAA agent. In addition, final results from the C-SWIFT study evaluating grazoprevir/elbasvir in combination with sofosbuvir 400mg in treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT1 or GT3 were presented as proof-of-concept for potentially shortening HCV treatment duration below 12 weeks. Data from these studies were presented at The International Liver CongressTM 2015 – the 50th annual congress of the European Association for the Study of the Liver.

 

 

Following 12 weeks of treatment with a combination of grazoprevir and elbasvir plus RBV, 96 percent of the patients (76/79) with chronic HCV GT1 infection who had failed prior treatment with specified DAA-based regimens achieved SVR12. Ninety four percent (32/34) of patients with compensated cirrhosis achieved SVR12. Virologic failure was reported for three patients in the trial. All three patients had resistance associated variants at baseline and relapsed after completion of study treatment.

Krishan Maggon 's insight:

Results of C-SALVAGE Study Showed High Sustained Virologic Response Rates in Patients Who Failed Prior Combination Therapy with Certain Direct Acting Antiviral (DAA) Agents

 

Results of C-SWIFT Study Provide Proof-of-Concept for Shorter Than Twelve Weeks Duration of Treatment with Triple-DAA Regimen in Patients with Chronic Hepatitis C Virus (HCV) Genotypes 1 and 3 Infection

 

 

Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and those on opiate substitution therapy.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Achillion ACH-3102/ACH-3422 Clinical Results International Liver Congress ILC 2015

Achillion ACH-3102/ACH-3422 Clinical Results International Liver Congress ILC 2015 | Hepatitis C New Drugs Review | Scoop.it
- Two late breaker presentations detail previously announced 100% SVR12 in Phase 2 trial evaluating 6- or 8-weeks of treatment with ACH-3102 and sofosbuvir in genotype 1 HCV patients and Phase 1 proof

 

LP06: Sustained virologic response after ACH-3102 and sofosbuvir treatment for 8 or 6 weeks: A phase 2 "proxy" study ACH102-017. ePoster Presentation, April 25, 3:30 pm CET, Hall B ePoster Area. Lead Author: Edward Gane.

As previously reported, 100% of patients achieved SVR12 after six- (n=12) or eight-weeks (n=12) of treatment in this ongoing interferon-free, ribavirin-free study evaluating the efficacy, safety, and tolerability of 50 mg of ACH-3102 and 400 mg of sofosbuvir, a marketed nucleotide polymerase inhibitor, in treatment-naïve genotype 1 HCV-infected patients.This represents the first study to report 100% SVR12 in patients with chronic GT-1 HCV infection using a two-drug combination for 6 weeks.Complete virologic responses were seen in all patients, including those who were considered harder to treat than others (i.e. GT-1a, non-CC and VL > 6 million IU/mL).The combination of ACH-3102 with sofosbuvir was well tolerated, with no treatment discontinuations, a low incidence of AEs, and no reported significant AEs or SAEs during the treatment and follow-up periods.The present study provides support for future studies which will explore the use of ACH-3102 in sofosbuvir-sparing regimens with short-treatment durations.In parallel, further studies will explore the combination of ACH-3102 and ACH-3422 (with and without sovaprevir, an NS3 protease inhibitor) in interferon- and ribavirin-free regimens with short treatment durations across different patient populations.

LP27: Gane, E., et al. ACH-3422, a novel nucleotide prodrug inhibitor of HCV NS5B polymerase. ePoster Presentation, April 25, 3:30 pm CET, Hall B ePoster Area. Lead Author: Edward Gane.

As previously announced, ACH-3422 achieved dose-related virologic responses in GT-1 HCV-infected patients. In the six patients who received 700 mg once daily for 14 days, mean maximal reduction from baseline was 4.6 log10, including three patients with target not detected.In all healthy volunteers and patients infected with HCV who received active treatment through 700 mg once daily, ACH-3422 was well-tolerated with no treatment-related serious adverse events, adverse event-related discontinuations, or clinically significant laboratory or ECG abnormalities.These results support further investigation of ACH-3422 with ACH-3102, a potent NS5A inhibitor, with or without the NS3/4A protease inhibitor sovaprevir, for the treatment of different patient populations with chronic HCV infection.
Krishan Maggon 's insight:

Two late breaker presentations detail previously announced 100% SVR12 in Phase 2 trial evaluating 6- or 8-weeks of treatment with ACH-3102 and sofosbuvir in genotype 1 HCV patients and Phase 1 proof-of-concept results with ACH-3422 -

- Clinical virology presentation continues to support improved barrier to resistance with ACH-3102 -

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

New Hepatitis C Treatments Have High Cure Rates for African Americans - AIDS.gov blog (blog)

New Hepatitis C Treatments Have High Cure Rates for African Americans - AIDS.gov blog (blog) | Hepatitis C New Drugs Review | Scoop.it
The epidemic of chronic hepatitis C virus (HCV) infection impacts over 3 million individuals in the United States, and over 50% of infected people are undiagnosed.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Merck Phase 3 C-EDGE Evaluating Grazoprevir/Elbasvir High SVR in Chronic Hepatitis C Virus Infection

Merck  Phase 3 C-EDGE  Evaluating Grazoprevir/Elbasvir High SVR in Chronic Hepatitis C Virus Infection | Hepatitis C New Drugs Review | Scoop.it

VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentations of data from the company’s ongoing C-EDGEpivotal Phase 3 clinical trial program evaluating the investigational once-daily tablet grazoprevir/elbasvir (100mg/50mg) in patients with or without cirrhosis who are infected with chronic hepatitis C virus (HCV) genotypes 1, 4 or 6 (GT1, 4 or 6).1 Patients in both the HCV infected, treatment-naïve (C-EDGE TN), and HIV/HCV co-infected, treatment-naïve (C-EDGE CO-INFXN) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95 percent (299/316 and 207/218, respectively). In addition, HCV infected, treatment-experienced patients (C-EDGE TE) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94 percent (98/104) and 92 percent (97/105), respectively, and those treated for 16 weeks achieved SVR12 rates of 97 percent (103/106) and 92 percent (97/105), respectively. These data were presented at The International Liver CongressTM 2015 – the 50th annual congress of the European Association for the Study of the Liver (Abstract #G07, E-Poster P0886 and E-Poster P0887). A paper detailing the findings of C-EDGE TN was published online in the Annals of Internal Medicine today.

Krishan Maggon 's insight:

C-EDGE TN Overview and Additional Findings

C-EDGE TN is a randomized, blinded, placebo-controlled trial evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks. Patients were randomized to an immediate treatment group that received grazoprevir/elbasvir for 12 weeks or to a deferred treatment group that received placebo for 12 weeks, were followed for an additional four weeks, and then received open label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included those patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of the 316 patients who received immediate treatment with grazoprevir/elbasvir, 50 percent were infected with GT1a, 42 percent with GT1b, six percent with GT4 and three percent with GT6. Overall, 22 percent of patients had liver cirrhosis.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Merck oral hepatitis C regimen shows 95 pct cure rate - Reuters

April 24 (Reuters) - Merck and Co Inc presentedtrial results on Friday showing that a once-daily combination oftwo experimental pills cured 95 percent of previously untreatedhepatitis C patients after...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

AbbVie Reveals FDA Priority Review For Investigational Therapy In Hepatitis C - Nasdaq

AbbVie Reveals FDA Priority Review For Investigational Therapy In Hepatitis C - Nasdaq | Hepatitis C New Drugs Review | Scoop.it
(RTTNews.com) - AbbVie (ABBV) Friday said the U.S. Food and Drug Administration has accepted its New Drug Application and granted priority review for
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Simeprevir/sofosbuvir (Janssen, Medivir) OPTIMIST trials: SVR12 97% HCV without cirrhosis, 84% in HCV with cirrhosis

Simeprevir/sofosbuvir (Janssen, Medivir) OPTIMIST trials: SVR12  97% HCV without cirrhosis, 84% in HCV with cirrhosis | Hepatitis C New Drugs Review | Scoop.it

Medivir AB (Nasdaq Stockholm: MVIR) announces that our partner Janssen Sciences Ireland UC, today publish positive results for simeprevir, the NS3/4A protease inhibitor for the treatment of hepatitis C virus (HCV) infection, at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) in Vienna. Late-breaking results from the phase III OPTIMIST-1 and OPTIMIST-2 trials highlight the clinical outcomes of simeprevir in an all-oral combination regimen in a wide range of patients with hepatitis C virus (HCV) infection.


The results from the OPTIMIST-1 and OPTIMIST-2 trials are the first phase III data to be presented on simeprevir in combination with sofosbuvir (SMV/SOF) in patients with genotype 1 chronic HCV infection, both with and without cirrhosis. Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

Krishan Maggon 's insight:
OPTIMIST-1 is a phase III, randomized, open-label trial to investigate the efficacy and safety of the all-oral regimen of SMV/SOF among treatment-naïve and treatment-experienced genotype 1 chronic HCV infected patients without cirrhosis. The primary objective was to show superior sustained virologic response (SVR) at 12 weeks after treatment (SVR12) with twelve and 8 weeks of treatment with SMV/SOF versus a historical control (patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon and ribavirin).

Ninety-seven (97) percent of patients treated with SMV/SOF for 12 weeks (n=150/155) achieved SVR12, which was superior to the SVR12 rate of 87 percent among the historical control.

- SVR12 rates of 100 percent were seen among patients with IL28B CC genotype (n=43/43) and those with baseline NS5A and NS3 Q80K polymorphisms (n=9/9).
OPTIMIST-2 is a phase III, open-label, single-arm trial to investigate the efficacy and safety of SMV/SOF in treatment-naïve and treatment-experienced genotype 1 chronic HCV infected patients with cirrhosis. The primary objective was to show superior SVR12 with twelve weeks of treatment with SMV/SOF versus a historical control.

Twelve (12) weeks of treatment with SMV/SOF resulted in SVR12 rates of 84 percent (n=86/103), which was superior to the SVR12 rate of 70 percent in the historical control.

Higher SVR12 rates were seen in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100 percent, n=13/13), patients with albumin ≥4 g/dL (94 percent; n=47/50), and treatment-naïve patients (88 percent; n=44/50).

The most common adverse events were fatigue (20 percent), headache (20 percent) and nausea (11 percent).
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus–infected patients - Chayama - 2015 - Hepatology - Wiley Online Library

Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus–infected patients - Chayama - 2015 - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it

Abstract

 

Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Patients in whom interferon (IFN)/ribavirin (RBV) therapy has failed remain at risk as effective therapeutic options are limited. This phase 2, randomized, open-label study evaluated an IFN- and RBV-free regimen of once-daily ombitasvir (ABT-267), an NS5A inhibitor, plus paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (paritaprevir/ritonavir), in pegylated IFN/RBV treatment–experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection. Patients without cirrhosis (aged 18-75 years) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks. Sustained virologic response (SVR) at posttreatment week 24 (SVR24) was the primary endpoint. Adverse events were collected throughout the study. One hundred ten patients received ≥1 dose of study medication. In the subtype 1b cohort, SVR24 rates were high (88.9%-100%) regardless of paritaprevir dose or treatment duration. In the genotype 2 cohort, SVR24 rates were 57.9% and 72.2% with 100 mg and 150 mg of paritaprevir, respectively. The SVR24 rate was higher in patients with subtype 2a (90%) than 2b (27%). Concordance between SVR12 and SVR24 was 100%. The most common adverse events overall were nasopharyngitis (29%) and headache (14%). Conclusion: In this difficult-to-treat population of patients in whom prior pegylated IFN/RBV had failed, ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection. (Hepatology2015;61:1523–1532)

Krishan Maggon 's insight:
Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus–infected patientsKazuaki Chayama1,*, Kazuo Notsumata2,Masayuki Kurosaki3, Ken Sato4, Lino Rodrigues Jr.5, Carolyn Setze5, Prajakta Badri5, Tami Pilot-Matias5, Regis A. Vilchez5 andHiromitsu Kumada6

Article first published online: 23 MAR 2015

DOI: 10.1002/hep.27705

© 2015 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Issue

Hepatology

Volume 61, Issue 5, pages 1523–1532, May 2015





Chayama, K., Notsumata, K., Kurosaki, M., Sato, K., Rodrigues, L., Setze, C., Badri, P., Pilot-Matias, T., Vilchez, R. A. and Kumada, H. (2015), Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus–infected patients. Hepatology, 61: 1523–1532. doi: 10.1002/hep.27705

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Interferon-free antiviral combination therapies without nucleosidic polymerase inhibitors - Journal of Hepatology

Interferon-free antiviral combination therapies without nucleosidic polymerase inhibitors - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it
Summary

The establishment of robust HCV cell culture systems and characterization of the viral life cycle provided the molecular basis for highly innovative, successful years in HCV drug development. With the identification of direct-acting antiviral agents (DAAs), such as NS3/4A protease inhibitors, NS5A replication complex inhibitors, nucleotide and non-nucleoside polymerase inhibitors, as well as host cell targeting agents, novel therapeutic strategies were established and competitively entered clinical testing. The first-in-class NS3/4A protease inhibitors telaprevir and boceprevir, approved in 2011, were recently outpaced by the pan-genotypic nucleotide polymerase inhibitor sofosbuvir that in combination with pegylated interferon and ribavirin, further shortens therapy durations and also offers the first interferon-free HCV treatment option. In the challenging race towards the goal of interferon-free HCV therapies, however, several oral DAA regimens without nucleotide polymerase inhibitors that combine a NS3/4A protease inhibitor, a NS5A inhibitor and/or a non-nucleoside polymerase inhibitor yielded competitive results. Second generation NS3/4A protease and NS5A inhibitors promise an improved genotypic coverage and a high resistance barrier. Results of novel DAA combination therapies without the backbone of a nucleotide polymerase inhibitor, as well as treatment strategies involving host targeting agents are reviewed herein.

Krishan Maggon 's insight:

J. Hepatology

November 2014Volume 61, Issue 1, Supplement, Pages S98–S107Interferon-free antiviral combination therapies without nucleosidic polymerase inhibitorsTania Mara Welzel, Georg Dultz, Stefan ZeuzemDepartment of Medicine 1, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyOpen AccessDOI: http://dx.doi.org/10.1016/j.jhep.2014.08.014
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Global epidemiology and genotype distribution of the hepatitis C virus infection - Journal of Hepatology

Global epidemiology and genotype distribution of the hepatitis C virus infection - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it

Summary

The treatment of chronic hepatitis C virus (HCV) infection has the potential to change significantly over the next few years as therapeutic regimens are rapidly evolving. However, the burden of chronic infection has not been quantified at the global level using the most recent data. Updated estimates of HCV prevalence, viremia and genotypes are critical for developing strategies to manage or eliminate HCV infection. To achieve this, a comprehensive literature search was conducted for anti-HCV prevalence, viraemic prevalence and genotypes for all countries. Studies were included based on how well they could be extrapolated to the general population, sample size and the age of the study. Available country estimates were used to develop regional and global estimates. Eighty-seven countries reported anti-HCV prevalence, while HCV viraemic rates were available for fifty-four countries. Total global viraemic HCV infections were estimated at 80 (64–103) million infections. Genotype distribution was available for ninety-eight countries. Globally, genotype 1 (G1) was the most common (46%), followed by G3 (22%), G2 (13%), and G4 (13%). In conclusion, the total number of HCV infections reported here are lower than previous estimates. The exclusion of data from earlier studies conducted at the peak of the HCV epidemic, along with adjustments for reduced prevalence among children, are likely contributors. The results highlight the need for more robust surveillance studies to quantify the HCV disease burden more accurately.

Krishan Maggon 's insight:

J. Hepatology

 

November 2014Volume 61, Issue 1, Supplement, Pages S45–S57

Global epidemiology and genotype distribution of the hepatitis C virus infectionErin Gower, Chris Estes, Sarah Blach, Kathryn Razavi-Shearer, Homie RazaviCenter for Disease Analysis, Louisville, CO, USAOpen AccessDOI: http://dx.doi.org/10.1016/j.jhep.2014.07.027

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

FDA Priority Review AbbVie Oral, Interferon-Free HCV Genotype 4 Therapy

FDA Priority Review AbbVie Oral, Interferon-Free HCV Genotype 4 Therapy | Hepatitis C New Drugs Review | Scoop.it

NORTH CHICAGO, Ill., April 24, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) has announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) and granted priority review for the company's, all-oral, interferon-free, two direct-acting antiviral treatment of ombitasvir, paritaprevir, ritonavir (OBV/PTV/r), with ribavirin (RBV). The NDA is for the treatment of adults with chronic genotype 4 (GT4) hepatitis C virus (HCV) infection.

AbbVie's regimen is the first all-oral, interferon-free therapy being evaluated by the FDA for patients in the United Stateswith chronic GT4 HCV infection. This submission affirms the company's commitment to seeking access to curative* therapy for patients living with chronic HCV infection (*curative is defined as when the virus is no longer detectable in the patient's blood 12 weeks after treatment ends; sustained virologic response [SVR12]).

The FDA granted priority review to AbbVie for the regimen based in part on data from the PEARL-I study, which was recently published online in The Lancet. The FDA grants priority review designation to investigational therapies that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. This designation shortens the regulatory review period for non-new chemical entity NDAs from the normal 10 months to six months. AbbVie's regimen was also granted a Breakthrough Therapy designation by the FDA on June 30, 2014, a status given to investigational treatments for serious or life-threatening conditions with preliminary clinical evidence that may demonstrate substantial improvement on at least one clinically significant endpoint compared to available therapy.1

Krishan Maggon 's insight:

THE NEW DRUG APPLICATION (NDA) WAS ACCEPTED BY THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) AND IS BASED ON RESULTS FROM THE PEARL-I STUDY, WHICH DEMONSTRATED UP TO 100 PERCENT SUSTAINED VIROLOGIC RESPONSE RATES AT 12 WEEKS POST-TREATMENT WITH NO DISCONTINUATIONS DUE TO ADVERSE EVENTS- FIRST ALL-ORAL, INTERFERON-FREE THERAPY BEING EVALUATED BY THE FDA FOR PATIENTS WITH CHRONIC GENOTYPE 4 (GT4) HEPATITIS C VIRUS (HCV) INFECTION- ABBVIE'S INVESTIGATIONAL REGIMEN HAS BEEN PREVIOUSLY DESIGNATED AS A BREAKTHROUGH THERAPY AND RECEIVED PRIORITY REVIEW BY THE FDA

 

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Gilead Sofosbuvir-Based Regimens Results in Chronic Hepatitis C Patients With Genotypes 2-5. ILC 2015

Gilead Sofosbuvir-Based Regimens Results in Chronic Hepatitis C Patients With Genotypes 2-5. ILC 2015 | Hepatitis C New Drugs Review | Scoop.it

VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi® (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver(The International Liver Congress™ 2015) in Vienna, Austria.


BOSON (Study GS-US-334-0153, #LB05), a randomized Phase 3 study of 592 patients, evaluated the safety and efficacy of Sovaldi plus RBV for 16 or 24 weeks compared with Sovaldi plus PEG/RBV for 12 weeks among treatment-naïve or treatment-experienced genotype 3 patients with and without cirrhosis and treatment-experienced genotype 2 patients with cirrhosis. Thirty-seven percent of study participants had cirrhosis.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

AbbVie Presents Late-Breaking, Preliminary Phase 3b Data with VIEKIRAX® + EXVIERA® in Chronic Hepatitis C Patients with Renal Impairment at The International Liver Congress™ 2015 - Apr 25, 2015

AbbVie Presents Late-Breaking, Preliminary Phase 3b Data with VIEKIRAX® + EXVIERA® in Chronic Hepatitis C Patients with Renal Impairment at The International Liver Congress™ 2015 - Apr 25, 2015 | Hepatitis C New Drugs Review | Scoop.it

VIENNA, April 25, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new, preliminary safety and efficacy data from the first cohort of its ongoing, Phase 3b RUBY-I study. RUBY-I is evaluating VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV) in treatment-naïve, non-cirrhotic, genotype 1 (GT1) chronic hepatitis C patients with severe renal impairment (stage 4 or 5), including those on hemodialysis. The primary endpoint of the study is the percentage of patients achieving sustained virologic response at 12 weeks post-treatment (SVR12). Patients who reached post-treatment week four to date (n=10 of 20 enrolled) achieved 100 percent SVR4 (n=10/10).1 RUBY-I was presented as a late-breaker today at The International Liver Congress™ (ILC) 2015, the 50th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

 

Additionally, RUBY-I data showed no virologic failures to date.1 Preliminary safety analyses reported that patients experienced mainly mild or moderate adverse events when receiving VIEKIRAX + EXVIERA with or without RBV, most commonly (>20 percent) anemia, fatigue, diarrhea, nausea, dizziness and headache.1 To date, eight of 13 genotype 1a (GT1a) patients had a RBV dose interruption.1

Krishan Maggon 's insight:

RUBY-I EVALUATES TREATMENT-NAÏVE, NON-CIRRHOTIC, GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS WITH SEVERE RENAL IMPAIRMENT- IN PRELIMINARY DATA FROM RUBY-I, PATIENTS RECEIVING VIEKIRAX + EXVIERA WITH OR WITHOUT RIBAVIRIN WHO REACHED POST-TREATMENT WEEK FOUR (N=10 OF 20 ENROLLED) ACHIEVED 100 PERCENT SUSTAINED VIROLOGIC RESPONSE AT FOUR WEEKS POST-TREATMENT (SVR4)1- ABBVIE'S PHASE 3B STUDIES EXPLORE VIEKIRAX + EXVIERA IN ADDITIONAL PATIENT POPULATIONS SEEN IN CLINICAL PRACTICE AND ACROSS MULTIPLE COUNTRIES AROUND THE WORLD

 

VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis. VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.

VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in GT1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.

Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Delaying HCV Tx Reduces Likelihood of Eradication - MedPage Today

Delaying HCV Tx Reduces Likelihood of Eradication - MedPage Today | Hepatitis C New Drugs Review | Scoop.it
During interferon era, postponing treatment made it hard to lower viral load.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

EU regulator EMA warn against combining hepatitis C drugs with amiodarone

EU regulator EMA warn against combining hepatitis C drugs with amiodarone | Hepatitis C New Drugs Review | Scoop.it
(Reuters) - European health regulators warned on Friday against using Gilead Sciences Inc's and Bristol-Myers Squibb Co's hepatitis C medicines along with amiodarone, a drug used to regulate the heartbeat...
Krishan Maggon 's insight:

EMA  

 

Concomitant use may increase risk of slow heart rate and related problems

The European Medicines Agancy (EMA) has confirmed a risk of severe bradycardia (slow heart rate) or heart block (problems with conduction of electrical signals in the heart) when the hepatitis C medicines Harvoni (sofosbuvir with ledipasvir) or a combination of Sovaldi (sofosbuvir) and Daklinza (daclatasvir) are used in patients who are also taking the medicine amiodarone, which is an antiarrhythmic (a medicine used to treat irregular heartbeat).

 

To manage this risk the Agency recommends that amiodarone should only be used in patients taking these hepatitis C medicines if other antiarrhythmics cannot be given. If concomitant use with amiodarone cannot be avoided, patients should be closely monitored. Because amiodarone persists for a long time in the body, monitoring is also needed if patients start such hepatitis C treatments within a few months of stopping amiodarone.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Conatus Clinical Results at EASL Meeting Support Emricasan Registration ... - CNNMoney

Conatus Clinical Results at EASL Meeting Support Emricasan Registration ... - CNNMoney | Hepatitis C New Drugs Review | Scoop.it

Conatus Clinical Results at EASL Meeting Support Emricasan 

 

SAN DIEGO, April 23, 2015 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) announced today that posters providing detailed results from four recently completed clinical trials of emricasan, the company's first-in-class, orally active pan-caspase protease inhibitor, are being presented this week at The International Liver Congress™ 2015, the 50th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria, April 22-26, 2015.

Results from the company's Phase 2 double-blind, placebo-controlled clinical trial of emricasan in patients with acute-on-chronic liver failure (ACLF), and Phase 2 double-blind, placebo-controlled clinical trial of emricasan in patients with nonalcoholic fatty liver disease (NAFLD), including the subset of NAFLD patients with nonalcoholic steatohepatitis (NASH), are addressed in two late-breaker posters:

Poster #LP35, entitled "A placebo-controlled, multicenter, double-blind, randomised, pharmacokinetic and pharmacodynamic trial of emricasan (IDN-6556) in subjects with acute-on-chronic liver failure (ACLF);" andPoster #LP37, entitled "A placebo-controlled, multicenter, double-blind, randomised trial of emricasan (IDN-6556) in subjects with non-alcoholic fatty liver disease (NAFLD) and raised transaminases."

A third poster addresses results from the company's Phase 1 trial in patients with mild, moderate and severe hepatic impairment and the company's Phase 1 trial in patients with severe renal impairment:

Poster #P0396, entitled "Emricasan, a potent pan-caspase inhibitor, rapidly reduces caspase activity and biomarkers of apoptosis in patients with hepatic impairment but not in healthy volunteers: implications for safety, selectivity and mechanism of action."

All three posters are available on the Events & Presentations page in the Investor Center of the Conatus website at www.conatuspharma.com.

Steven J. Mento, Ph.D., President and Chief Executive Officer of Conatus, said, "Emricasan has demonstrated the potential to address the full spectrum of liver disease across a broad range of etiologies and disease severity. Conatus is initially focusing on the treatment of cirrhosis, particularly NASH-driven cirrhosis. The results from our clinical development activities in 2014 are paving the way for our emricasan registration strategy. Our ACLF and organ impairment trials defined safe and effective dosing of emricasan in patients with cirrhosis, including those with liver function impairment. Our NAFLD/NASH trial confirmed that the optimal dose of emricasan is consistent across different etiologies. With a comprehensive data package that includes the results we are presenting at the EASL meeting, we are now preparing to meet with regulatory authorities to seek specific guidance on the appropriate endpoints that could support regulatory approval, in particular surrogate endpoints that could be used in accelerated approval pathways."

Conatus intends to include NASH-driven cirrhosis in its initial registration strategy for emricasan. This population already represents a high unmet medical need that is expected to continue growing in the years ahead. Importantly, three validated surrogate markers of mortality risk were identified for this segment of liver disease patients in a manuscript co-authored by the American Association for the Study of Liver Diseases (AASLD) and the U.S. Food and Drug Administration (FDA), and accepted in January 2015 for publication in the scientific journal Hepatology:

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Cancer rates among patients with hepatitis C are increased compared to those not infected

Cancer rates among patients with hepatitis C are increased compared to those not infected | Hepatitis C New Drugs Review | Scoop.it
Results announced today at The International Liver Congress 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Biotest Pharma Civacir®(hepatitis C immune globulin HCIG) Phase III data ILC 2015

Biotest Pharma  Civacir®(hepatitis C immune globulin HCIG)  Phase III data ILC 2015 | Hepatitis C New Drugs Review | Scoop.it

Biotest Pharmaceuticals Corporation 

 

Data presented at the congress are phase III clinical study data. The study is a randomized, open-label trial conducted in 24 clinical centers in the United States.

All patients in the study received antiviral treatment prior to transplantation, mainly new recently approved antivirals. Patients who were  treated with the study drug Civacir® obtained either 200 mg/kg or 300 mg/kg body weight during and immediately after transplantation. The control group received the standard of care (no antiviral treatment after transplantation).

The clinical data shows that 1 out of 21 (5%) reinfection was observed in the high dose group. In contrast 6 out of 20 (30%) and 7 out of 22 (32%) reinfections occurred in the low dose and control group, respectively. Civacir® has been well tolerated and no serious adverse events were related to the study drug. More than two-thirds of the planned patients have been enrolled in the ongoing clinical trial.


“Civacir® represents a novel prophylactic approach to prevent hepatitis C virus recurrence in liver transplant recipients. If the presented results are also confirmed after the conclusion of the study, this would be a relevant therapy option for the treatment of transplant patients with hepatitis C.” said Dr. Bernhard Ehmer, CEO of Biotest AG.

Krishan Maggon 's insight:

New data from an ongoing Phase III trial revealed today at The International Liver CongressTM 2015 show that the use of hepatitis C immune globulin (HCIG, Civacir®) can effectively prevent hepatitis C virus (HCV) recurrence in patients following a liver transplant (LT). The data demonstrate that intravenous Civacir given both peri- and post-LT prevents HCV-reinfection in patients who also received antiviral therapy (AVT) before their transplant operation.

 

Civacir is a hepatitis C immune globulin (HCIG) produced from pooled plasma from hundreds of screened donors who have high antibody titers against HCV.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Gilead’s Hepatitis C Combo Cuts Cure to Six Weeks, Fails at Four

Gilead’s Hepatitis C Combo Cuts Cure to Six Weeks, Fails at Four | Hepatitis C New Drugs Review | Scoop.it
RT @hcvresearchnews: Gilead’s Hepatitis C Combo Cuts Cure to Six Weeks, Fails at Four http://t.co/DN5oRuDql7 via @business #HCV #ILC2015 #L…

 

Gilead Sciences Inc.’s experimental hepatitis C combination cured 93 percent of previously untreated patients after six weeks of therapy, potentially shortening treatment times compared to the drugmaker’s current therapy.

Patients in the midstage trial received a combination of Sovaldi, Gilead’s already-approved medicine, with the experimental drugs GS-5816 and GS-9857.

Four-week-long treatment with the experimental combination wasn’t successful, and the cure rate in that part of the trial was only 27 percent, according to data presented at the European Association for the Study of the Liver conference in Vienna.

Krishan Maggon 's insight:

Gilead high SVR of 93% with 6 weeks  of treatment cuts cost of HCV drug therapy. 

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Merck and Gilead square off in battle of the next-next-gen hep C combos - FierceBiotech

Merck and Gilead square off in battle of the next-next-gen hep C combos - FierceBiotech | Hepatitis C New Drugs Review | Scoop.it
Early today both Gilead and Merck issued new data on their next-next-gen hepatitis C combos, demonstrating just how brutal the competition for market share is becoming while highlighting some of the boundaries that are emerging in shortening...
more...
No comment yet.