title: Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis.
abstract: Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the nonnucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naive patients with HCV genotype 1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (n=362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times-daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W and BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0 to F2 versus F3 to F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3 to F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in rates of sustained virologic response 12 weeks after completion of treatment (SVR12) between patients with mild to moderate fibrosis (F0 to F2) versus F3 to F4 did not show a consistent pattern and were not statistically significant (63% versus 47% for TID16W, 53% versus 76% for TID28W, 48% versus 67% for TID40W, 70% versus 67% for BID28W, and 40% versus 36% for TID28W-NR, respectively; P > 0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01132313.).
authors.affiliation: J. W. Goethe University Hospital, Frankfurt, Germany zeuzem@em.uni-frankfurt.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Hospital Carlos III, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, INSERM UMR S 1149, CRI, Université Paris Diderot, DHU UNITY, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Auckland Clinical Studies, Auckland, New Zealand.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.affiliation: INSERM 954, Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Austin Health, Heidelberg, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Angus
authors.affiliation: University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: University of Bern, Bern, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.affiliation: University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Alfred Hospital, Melbourne, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.affiliation: University Hospital Mainz, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.affiliation: Medical School of Hannover, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.affiliation: Hôpital Saint Joseph, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: Hospital Universitario Valle Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Gallivan
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Voss
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Sabo
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Wulf
authors.initials: W
authors.lastname: Böcher
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
authors.forename: Federico J
authors.initials: FJ
authors.lastname: Mensa
mesh_terms: D000179:Acrylates / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000179:Acrylates; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D001562:Benzimidazoles; D009842:Oligopeptides; D011804:Quinolines; D013844:Thiazoles; D012254:Ribavirin; C000592437:deleobuvir; C552340:faldaprevir; D011392:Proline; D007930:Leucine