title: HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127) and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection.
abstract: The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2) in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including those ineligible for peginterferon (HCVerso2). Patients without cirrhosis were randomized to 16 weeks (Arm 1; n=208 HCVerso1, n=213 HCVerso2) or 24 weeks (Arm 2; n=211 in both studies) of faldaprevir + deleobuvir + ribavirin. Patients with compensated cirrhosis received open-label faldaprevir + deleobuvir + ribavirin for 24 weeks (Arm 3; n=51, n=72). Primary endpoints were comparisons of adjusted sustained virologic response (SVR) rates with historical rates: 71% (HCVerso1) and 68% (HCVerso2). Adjusted SVR12 rates were significantly greater than historical controls for Arms 1 and 2 in HCVerso2 (76%, 95% confidence interval [CI] 71-81,P=0.002; 81%, 95% CI 76-86,P<0.0001) and Arm 2 in HCVerso1 (81%, 95% CI 77-86,P<0.0001), but not for Arm 1 of HCVerso1 (72%, 95% CI 66-77,P=0.3989). Unadjusted SVR12 rates in Arms 1, 2, and 3 were 71.6%, 82.5%, and 72.5%, respectively, in HCVerso1 and 75.6%, 82.0%, and 73.6%, respectively, in HCVerso2. Virologic breakthrough and relapse occurred in 24-week arms in 8%-9% and 1% of patients, respectively, and in 16-week arms in 7%-8% and 9%-11% of patients, respectively. The most common adverse events were nausea (46%-61%) and vomiting (29%-35%). Adverse events resulted in discontinuation of all medications in 6%-8% of patients. In treatment-naïve patients with hepatitis C virus genotype-1b infection, with or without cirrhosis, faldaprevir + deleobuvir + ribavirin treatment for 24 weeks resulted in adjusted SVR12 rates significantly higher than historical controls. Both studies were registered in ClinicalTrials.gov (NCT01732796, NCT01728324).
authors.affiliation: Department of Internal Medicine 1, JW Goethe University Hospital, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Department of Infectious and Tropical Diseases, University of Brescia, Brescia.
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.affiliation: Department of Medical and Surgical Sciences, Università di Bologna and Azienda Ospedaliero-Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
authors.affiliation: Department of Internal Medicine, Hospital Universitari Vall d'Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: University Paris Descartes, Department of Hepatology, Hospital Cochin, APHP and INSERM UMS-20, Institut Pasteur, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Department of Gastroenterology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Calinas
authors.affiliation: Department of Infectious Diseases, AO Ospedale Niguarda Cà Granda, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.affiliation: Liver Unit, Hospital Universitario La Paz, CIBERehd, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Olveira
authors.affiliation: Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Shiffman
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.affiliation: Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roehrle
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslanyan
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Vinisko
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: Federico J
authors.initials: FJ
authors.lastname: Mensa
authors.affiliation: Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
keywords: NS3 protease inhibitor; antiviral; chronic hepatitis C; cirrhosis; nonnucleoside polymerase inhibitor