Journal ArticleDOI
Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial
Stefan Zeuzem,Reem Ghalib,K. Rajender Reddy,Paul J. Pockros,Ziv Ben Ari,Yue Zhao,Deborah D. Brown,Shuyan Wan,Mark J. DiNubile,Bach-Yen Nguyen,Michael N. Robertson,Janice Wahl,Eliav Barr,Joan R. Butterton +13 more
TLDR
Grazoprevir and elbasvir were evaluated in a randomized, blinded, placebo-controlled trial in treatment-naive patients with hepatitis C virus (HCV) infection.Abstract:
BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.read more
Citations
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EASL Recommendations on Treatment of Hepatitis C
Jean-Michel Pawlotsky,Alessio Aghemo,Geoffrey Dusheiko,Xavier Forns,Massimo Puoti,Christophe Sarrazin +5 more
TL;DR: The optimal management of patients with acute and chronic HCV infections in 2018 and onwards is described, as well as developments in diagnostic procedures and improvements in therapy and prevention.
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Approved Antiviral Drugs over the Past 50 Years
TL;DR: This paper presents for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.
Journal ArticleDOI
Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study.
David Roth,David R. Nelson,Annette Bruchfeld,AnnMarie Liapakis,Marcelo Silva,Howard Paul Monsour,Paul J. Martin,Stanislas Pol,Maria Carlota Londoño,Tarek Hassanein,Philippe J. Zamor,Eli Zuckerman,Shuyan Wan,Beth Jackson,Bach-Yen Nguyen,Michael N. Robertson,Eliav Barr,Janice Wahl,Wayne Greaves +18 more
TL;DR: Once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease.
Journal ArticleDOI
EASL recommendations on treatment of hepatitis C: Final update of the series ☆
Jean-Michel Pawlotsky,Francesco Negro,Alessio Aghemo,Marina Berenguer,Olav Dalgard,Geoffrey Dusheiko,Fiona Marra,Massimo Puoti,Heiner Wedemeyer +8 more
TL;DR: These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
Journal ArticleDOI
Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review
Oluwaseun Falade-Nwulia,Catalina Suarez-Cuervo,David R. Nelson,Michael W. Fried,Jodi B Segal,Mark S. Sulkowski +5 more
TL;DR: In this article, the authors summarize published literature on the efficacy and safety of oral direct-acting antiviral (DAA) regimens for treatment of persons with chronic hepatitis C virus (HCV) infection.
References
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Journal ArticleDOI
Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More
TL;DR: Chronic HCV infection is curable with SVR attainment, and with cure comes improved liver histology and more favorable clinical outcomes, in comparison with patients who do not achieve the same therapeutic milestone.
Journal ArticleDOI
Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial
Eric Lawitz,Edward Gane,Brian L. Pearlman,Edward Tam,Wayne Ghesquiere,Dominique Guyader,Laurent Alric,Jean-Pierre Bronowicki,Laura Lester,William Sievert,Reem Ghalib,Luis A. Balart,Fredrik Sund,Martin Lagging,Frank J. Dutko,Melissa Shaughnessy,Peggy Hwang,Anita Y. M. Howe,Janice Wahl,Michael N. Robertson,Eliav Barr,Barbara Haber +21 more
TL;DR: The C-WORTHY trial as mentioned in this paper was a randomized, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin in patients with hepatitis C virus (HCV) genotype 1 infection with baseline characteristics of poor response.
Journal ArticleDOI
Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial
Christophe Hézode,Tarik Asselah,K. Rajender Reddy,Tarek Hassanein,Marina Berenguer,Katarzyna Fleischer-Stępniewska,Patrick Marcellin,Coleen Hall,Gretja Schnell,Tami Pilot-Matias,N. Mobashery,Rebecca Redman,Regis A. Vilchez,Stanislas Pol +13 more
TL;DR: This study examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir, given with or without ribavirin, in patients infected with genotype 4 of Hepatitis C virus.
Journal ArticleDOI
Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial
Mark S. Sulkowski,Christophe Hézode,Jan Gerstoft,John M. Vierling,Josep Mallolas,Stanislas Pol,Marcelo Kugelmas,Abel Murillo,Nina Weis,Ronald Nahass,Oren Shibolet,Lawrence Serfaty,Marc Bourlière,Edwin DeJesus,Eli Zuckerman,Frank J. Dutko,Melissa Shaughnessy,Peggy Hwang,Anita Y. M. Howe,Janice Wahl,Michael N. Robertson,Eliav Barr,Barbara Haber +22 more
TL;DR: The C-WORTHY trial as mentioned in this paper evaluated the efficacy and safety of a combination of grazoprevir plus elbasvir with or without ribavirin in patients with hepatitis C virus (HCV) mono-infection and co-infected patients.
Journal ArticleDOI
MK-5172, a Selective Inhibitor of Hepatitis C Virus NS3/4a Protease with Broad Activity across Genotypes and Resistant Variants
Vincenzo Summa,Steven W. Ludmerer,John A. Mccauley,Christine Fandozzi,Christine Burlein,Giuliano Claudio,Paul J. Coleman,Jillian DiMuzio,Marco Ferrara,Marcello Di Filippo,Adam Gates,Donald J. Graham,Steven Harper,Daria J. Hazuda,Carolyn McHale,Edith Monteagudo,Vincenzo Pucci,Michael Rowley,Michael T. Rudd,Aileen Soriano,Mark W. Stahlhut,Joseph P. Vacca,David B. Olsen,Nigel J. Liverton,Steven S. Carroll +24 more
TL;DR: The preclinical profile of MK-5172 is reported, a novel P2-P4 quinoxaline macrocyclic NS3/4a protease inhibitor currently in clinical development that is anticipated to be broadly active against multiple HCV genotypes and clinically important resistance variants and highly suited for incorporation into newer all-oral regimens.
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