studies

314A AASLD ABSTRACTS HEPATOLOGY, October, 2015
206
Daclatasvir plus sofosbuvir with or without ribavirin in
genotype 3 patients from a large French multicenter
compassionate use program
Christophe Hezode 1 , Victor de Ledinghen 2 , Hélène Fontaine 3 ,
Fabien Zoulim 4 , Pascal Lebray 5 , Nathalie Boyer 6 , Dominique
G. Larrey 7 , Christine Silvain 8 , Danielle Botta-Fridlund 9 , Vincent
Leroy 10,11 , Marc Bourlière 12 , Louis d’Alteroche 13 , Isabelle
Fouchard-Hubert 14 , Dominique Guyader 15 , Isabelle Rosa 16 , Eric
Nguyen-Khac 17 , Vincent Di Martino 18 , Fabrice Carrat 19 , Larysa
Fedchuk 20 , Raoudha Akremi 20 , Yacia Bennai 20 , Jean-Pierre Bronowicki
21 ; 1 Department of Hépato-Gastroenterology, CHU Henri
Mondor, Créteil, France; 2 Liver fibrosis investigational center, Haut-
Lévêque Hospital, Bordeaux University Hospital, Pessac, France;
3 Department of Hepatology, Cochin Hospital, APHP, Paris, France;
4 Department of Hepatology, La Croix-Rousse Hospital, Lyon Civil
Hospices, Lyon, France; 5 Department of Hepato-Gastroenterology,
Pitié Salpêtrière Hospital, Paris, France; 6 Department of Hepatology,
Beaujon Hospital, APHP, Paris, France; 7 Department of
Hepato-Gastroenterology, Saint-Eloi Hospital, CHU Montpellier,
Montpellier, France; 8 Department of Hepato-Gastroenterology
and of nutritional support, epithelial tissues and cytokines laboratory
EA 4331, CHU Poitiers, Poitiers, France; 9 Department
of Hepato-Gastroenterology, Conception Hospital, Marseille,
France; 10 Grenoble University hospital, Hepato-Gastroenterology
University Clinic, Grenoble, France; 11 Inserm, 823 Unity, Grenoble,
France; 12 Department of Hepatology and Gastroenterology,
Saint-Joseph Hospital, Marseille, France; 13 Unit of Hepatology,
Department of Hepato-Gastroenterology, CHU Trousseau, Tours,
France; 14 Department of Hepato-Gastroenterology, CHU Angers,
Angers, France; 15 Department of liver diseases, CHU Rennes,
Rennes 1 University, Rennes, France; 16 Department of Hepatology
and Gastroenterology, CHI Créteil, Créteil, France; 17 Department
of Hepato-Gastroenterology, CHU Amiens Nord, Amiens, France;
18 Department of Hepatology and of digestive intensive care unit,
CHRU Jean Minjoz, Besançon, France; 19 Inserm UMR-S 707,
Pierre-et-Marie-Curie University Paris 6, Paris, France; 20 Bristol-Myers
Squibb Research and Development, Rueil-Malmaison, France;
21 INSERM Unité 954, CHU Nancy and Lorraine University, Vandoeuvre-lès-Nancy,
France
Background and aims. Treatment options for HCV genotype 3
(GT3) patients are limited. The combination daclatasvir (DCV)
and sofosbuvir (SOF) for 12 weeks is associated with high
SVR 12
rate in genotype 3 non cirrhotic patients (96%) and a
lower SVR 12
rate in cirrhotic (70%). GT3 cirrhotic remain a
difficult to treat population and may benefit from the addition
of ribavirin (RBV) or extended treatment duration. This analysis
reports SVR results from an ongoing multicenter compassionate
use program (ATU) in France. Methods. Patients with GT3 and
advanced liver disease from 221 centers have been included
since March 2014 to October 2014. Transplanted patients
were excluded from this analysis. All patients received DCV+-
SOF QD for 12 or 24 weeks, with RBV added at the physician’s
discretion. We report interim SVR 12
rates in patients who have
completed treatment to date and for whom at least one follow-up
visit was available. Results. 395 patients were enrolled
with the following characteristics: males (75.5%), median
age (54.4 years; 27-83), HCV mono-infected (80%), cirrhosis
(n=322; 81.5%), including Child-Pugh A (85.5%), B (11.5%),
C (3.0%) and treatment-experienced (n=288; 73.1%). Median
HCV-RNA was 5.99 (1.20; 7.41) log IU/mL and median platelets
count was 120.0 x10 9 /L (30-387). 71.6% of patients have
albumin≥ 35 g/L. RBV was given in 20.5% of patients and
treatment duration was 24 weeks in 42.0% and 12 weeks in
17.5%. Data on SVR 12
is available in 78 patients; SVR 12
was
achieved in 90% (70/78). SVR 12
rates according to treatment
schedule and fibrosis stage are presented in the table. The
treatment failures were related to relapse in 6 patients and
unknown reasons in 2 patients (only D0 and SVR 12
available).
No virologic breakthrough was observed. Treatment discontinuations
were related to: 1 adverse event, 4 deaths not related
to study drugs, 1 patient’s decision, 1 treatment failure and 4
for unknown reason. Efficacy and safety data will be updated
and presented in the 395 patients at the congress. CONCLU-
SION: DCV+SOF±RBV regimen demonstrated high SVR 12
rate
in GT3 patients with advanced liver disease. The optimal treatment
duration was 24 weeks in cirrhotic patients. The impact of
RBV will be analyzed in the overall population and presented
at the meeting.
Efficacy of DCV+SOF±RBV regimens in GT3 patients
Disclosures:
Christophe Hezode - Speaking and Teaching: Roche, BMS, MSD, Janssen, abbvie,
Gilead
Victor de Ledinghen - Board Membership: Janssen, Gilead, BMS, Abbvie; Speaking
and Teaching: AbbVie, Merck, BMS, Gilead
Hélène Fontaine - Board Membership: Abbvie, Gilead, BMS, Janssen; Independent
Contractor: gilead, BMS, MSD, Roche, Janssen
Fabien Zoulim - Advisory Committees or Review Panels: Janssen, Gilead, Novira,
Abbvie, Tekmyra, Transgene; Consulting: Roche; Grant/Research Support:
Novartis, Gilead, Scynexis, Roche, Novira, Assemblypharm; Speaking and
Teaching: Bristol Myers Squibb, Gilead
Pascal Lebray - Grant/Research Support: Merck, astellas, Biotest, BMS; Speaking
and Teaching: Janssen, MSD, Gilead
Nathalie Boyer - Board Membership: MSD, JANSSEN, Gilead, Abbvie; Speaking
and Teaching: BMS
Dominique G. Larrey - Advisory Committees or Review Panels: BAYER, SANOFI,
PFIZER, SERVIER-BIG, AEGERION, MMV, BIAL-QUINTILES, TEVA, ORION, NEG-
MA-LERADS, ASTELLAS, ASTRAZENECA, DNDI, GSK, J AND J; Board Membership:
BMS, GILEAD, ABBVIE, BMS, GILEAD, ITREAS, MMS; Grant/Research
Support: GILEAD, MSD, BMS, ABBVIE, TIBOTEC/JANSSEN, BMS
Danielle Botta-Fridlund - Consulting: GILEAD, ABBVIE, BMS, MSD
Vincent Leroy - Board Membership: Abbvie, BMS, Gilead; Consulting: Janssen,
MSD; Speaking and Teaching: Abbvie, BMS, Gilead, Janssen, MSD
Marc Bourlière - Advisory Committees or Review Panels: Schering-Plough,
Bohringer inghelmein, Schering-Plough, Bohringer inghelmein, Transgene; Board
Membership: Bristol-Myers Squibb, Gilead, Idenix; Consulting: Roche, Novartis,
Tibotec, Abott, glaxo smith kline, Merck, Bristol-Myers Squibb, Novartis, Tibotec,
Abott, glaxo smith kline; Speaking and Teaching: Gilead, Roche, Merck, Bristol-Myers
Squibb
Isabelle Fouchard-Hubert - Speaking and Teaching: JANSSEN, BMS, GILEAD,
ABBVIE
Dominique Guyader - Advisory Committees or Review Panels: ROCHE, GILEAD,
IRIS, ABBVIE; Board Membership: MERCK; Grant/Research Support: JANSSEN;
Speaking and Teaching: BMS
Eric Nguyen-Khac - Speaking and Teaching: Gilead, Abbvie, Janssen, Roche,
MSD, BMS
Vincent Di Martino - Advisory Committees or Review Panels: Gilead, France,
Abbvie, BMS France; Board Membership: MSD France; Consulting: Gilead,
France; Speaking and Teaching: Janssen, BMS France, Gilead France
Fabrice Carrat - Advisory Committees or Review Panels: BMS; Grant/Research
Support: Janssen, Merck, Gilead, BMS, Roche
Larysa Fedchuk - Employment: Bristol-Myers Squibb
Raoudha Akremi - Employment: BMS
Jean-Pierre Bronowicki - Consulting: Merck, Janssen, Boehringer Ingelheim, Gilead,
BMS, Bayer, Novartis, GSK, Merck, Janssen, Boehringer Ingelheim, Gilead,
BMS, Bayer, Novartis, GSK, ABBVIE, ABBVIE; Speaking and Teaching: Roche,
Merck, Janssen, BMS, Bayer, Roche, Merck, Janssen, BMS, Bayer, ABBVIE
The following authors have nothing to disclose: Christine Silvain, Louis d’Alteroche,
Isabelle Rosa, Yacia Bennai