ORAL PRESENTATIONS Conclusions: TSU-68 combined with repeated cTACE did not improve OS. However, favourable TTTF was observed in patients with low VEGF-C and those with BCLC-B HCC receiving TSU68. Further study is needed to confirm the potential of VEGF-C as a predictive marker. TSU-68 treatment was tolerable in HCC patients receiving repeated TACE with a high safety profile and long treatment duration of 1 year.
Viral hepatitis C: Therapy
O001 C-SALVAGE: GRAZOPREVIR (GZR; MK-5172), ELBASVIR (EBR; MK-8742) AND RIBAVIRIN (RBV) FOR CHRONIC HCV-GENOTYPE 1 (GT1) INFECTION AFTER FAILURE OF DIRECT-ACTING ANTIVIRAL (DAA) THERAPY 1
2
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X. Forns , S. Gordon , E. Zuckerman , E. Lawitz , M. Buti , J. Calleja Panero6 , H. Hofer7 , C. Gilbert8 , J. Palcza8 , A. Howe8 , M. DiNubile8 , M. Robertson8 , J. Wahl8 , E. Barr8 , J. Sullivan-Bolyai8 . 1 IDIBAPS and CIBEREHD, Barcelona, Spain; 2 Henry Ford Health System, Detroit, United States; 3 Carmel Medical Center, Haifa, Israel; 4 The Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States; 5 Hospital Universitario Valle Hebron and Ciberehd, Barcelona, 6 Hospital University Puerta de Hierro Majadahonda, Madrid, Spain; 7 Medical University of Vienna, Vienna, Austria; 8 Merck & Co., Inc., Whitehouse Station, United States E-mail: [email protected] Background and Aims: Treatment options are needed for patients who do not achieve SVR on regimens containing DAAs. The Phase-2 C-SALVAGE study investigated the safety and efficacy of an interferon-free combination of GZR [NS3/4A protease inhibitor (PI)] and EBR [NS5A inhibitor] with RBV for patients with chronic HCV GT1 infection who had failed licensed DAA-containing therapy. Methods: C-SALVAGE is an international open-label study of GZR 100 mg QD, EBV 50 mg QD, and weight-based RBV BID for 12 weeks in patients with chronic HCV GT1 infection who had failed ≥4 weeks of peginterferon and RBV combined with boceprevir, telaprevir, simeprevir, or sofosbuvir. Per protocol, ~80% of the enrolled subjects were to have experienced virologic failure. Exclusion criteria included decompensated liver disease, hepatocellular carcinoma, HIV or HBV co-infection, thrombocytopenia 1.00 remained effective but diminished in the morbidity risk reduction achieved [30%]. This is not the case if treatment initiation is delayed until after FIB4 >3.25. The risk reductions associated with treatment initiation before FIB4 >3.25 were 34% for the composite event and 45% for death but if initiated after FIB4 >3.25 were only 11% and 25%, respectively. These detrimental effects of delaying treatment until FIB4 >3.25 were due to a reduction in the likelihood that treated patients would achieve viral load suppression and a reduced impact of viral load suppression on morbidity. Conclusions: Delaying treatment until after a patient’s FIB4 level exceeds 3.25 has a clear detrimental effect on treatment effectiveness
O004 ON-TREATMENT VIROLOGIC RESPONSE AND TOLERABILITY OF SIMEPREVIR, DACLATASVIR AND RIBAVIRIN IN PATIENTS WITH RECURRENT HEPATITIS C VIRUS GENOTYPE 1b INFECTION AFTER ORTHOTOPIC LIVER TRANSPLANTATION (OLT): INTERIM DATA FROM THE PHASE II SATURN STUDY X. Forns1 , M. Berenguer2 , K. Herzer3 , M. Sterneck4 , M.F. Donato5 , P. Andreone6 , S. Fagiuoli7 , T. Cieciura8 , M. Durlik8 , J.L. Calleja9 , Z. Marino ˜ 1 , A. Simion10 , U. Shukla11 , T. Verbinnen10 , O. Lenz10 , S. Ouwerkerk-Mahadevan12 , M. Peeters10 , R. Kalmeijer11 , J. Witek11 . 1 Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, 2 Department of Digestive Diseases, Hepatology and Liver Transplantation Unit, La Fe University Hospital and CIBEREHD, Valencia, Spain; 3 Department for Gastroenterology and Hepatology, University Hospital Essen, Essen, 4 Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 5 Division of Digestive Diseases, IRCCS Maggiore Hospital, Milan, 6 Department of Medical and Surgical Sciences, University of Bologna, Bologna, 7 Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy; 8 Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland; 9 Department of Gastroenterology and Hepatology, University Hospital Puerta de Hierro Mahadahonda, Madrid, Spain; 10 Janssen Infectious Diseases BVBA, Beerse, Belgium; 11 Janssen Research & Development LLC, Titusville, NJ, United States; 12 Janssen Research and Development, Beerse, Belgium E-mail: [email protected] Background and Aims: Simeprevir (SMV) and daclatasvir (DCV) are approved for the treatment of hepatitis C virus (HCV) infection in the non-transplant setting. SMV is a NS3/4A protease inhibitor and DCV is a NS5A replication complex inhibitor. The combination of SMV+DCV±ribavirin (RBV) has been previously evaluated in treatment-naïve and prior null responder patients (pts; LEAGUE-1). SATURN is an ongoing open-label Phase II study, investigating SMV+DCV+RBV in pts with recurrent HCV genotype 1b infection after orthotopic liver transplantation (OLT). Virologic response and tolerability results are presented from a pre-planned interim analysis. Methods: Post-OLT treatment-naïve or -experienced (prior relapser, partial or null responder to peginterferon±RBV) adults on stable immunosuppressive therapy following OLT were included. Part 1 (P1) included pts with METAVIR score F1–F2 on cyclosporine (CsA) or tacrolimus (TAC). Part 2 (P2) included F1–F4 pts on TAC. Pts received SMV (150 mg once daily [QD]), DCV (60 mg QD) and RBV (1–1.2 g/day) for 24 weeks. At the time of analysis, all P1 pts had reached end of treatment (EOT) and in P2, Week 4 of treatment (or early discontinuation). Analyses were based on the intent-to-treat population. Results: A total of 21 (P1) and 14 (P2) pts were included (P1/P2: female, 33%/43%; median age, 63.0 years [y]/59.5 y; mean time since transplantation, 3.98 y/5.36 y; median baseline HCV RNA 6.9 log10 /6.9 log10 IU/mL; METAVIR F3/F4, 0%/57%). P1 CsA pts had ~6-fold higher SMV plasma concentrations leading to SMV dose adjustment and exclusion of CsA pts from P2. On-treatment virologic response is shown in the Table. In P1, 91% of pts had HCV RNA
Viral hepatitis C: Therapy
O001 C-SALVAGE: GRAZOPREVIR (GZR; MK-5172), ELBASVIR (EBR; MK-8742) AND RIBAVIRIN (RBV) FOR CHRONIC HCV-GENOTYPE 1 (GT1) INFECTION AFTER FAILURE OF DIRECT-ACTING ANTIVIRAL (DAA) THERAPY 1
2
3
4
5
X. Forns , S. Gordon , E. Zuckerman , E. Lawitz , M. Buti , J. Calleja Panero6 , H. Hofer7 , C. Gilbert8 , J. Palcza8 , A. Howe8 , M. DiNubile8 , M. Robertson8 , J. Wahl8 , E. Barr8 , J. Sullivan-Bolyai8 . 1 IDIBAPS and CIBEREHD, Barcelona, Spain; 2 Henry Ford Health System, Detroit, United States; 3 Carmel Medical Center, Haifa, Israel; 4 The Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States; 5 Hospital Universitario Valle Hebron and Ciberehd, Barcelona, 6 Hospital University Puerta de Hierro Majadahonda, Madrid, Spain; 7 Medical University of Vienna, Vienna, Austria; 8 Merck & Co., Inc., Whitehouse Station, United States E-mail: [email protected] Background and Aims: Treatment options are needed for patients who do not achieve SVR on regimens containing DAAs. The Phase-2 C-SALVAGE study investigated the safety and efficacy of an interferon-free combination of GZR [NS3/4A protease inhibitor (PI)] and EBR [NS5A inhibitor] with RBV for patients with chronic HCV GT1 infection who had failed licensed DAA-containing therapy. Methods: C-SALVAGE is an international open-label study of GZR 100 mg QD, EBV 50 mg QD, and weight-based RBV BID for 12 weeks in patients with chronic HCV GT1 infection who had failed ≥4 weeks of peginterferon and RBV combined with boceprevir, telaprevir, simeprevir, or sofosbuvir. Per protocol, ~80% of the enrolled subjects were to have experienced virologic failure. Exclusion criteria included decompensated liver disease, hepatocellular carcinoma, HIV or HBV co-infection, thrombocytopenia 1.00 remained effective but diminished in the morbidity risk reduction achieved [30%]. This is not the case if treatment initiation is delayed until after FIB4 >3.25. The risk reductions associated with treatment initiation before FIB4 >3.25 were 34% for the composite event and 45% for death but if initiated after FIB4 >3.25 were only 11% and 25%, respectively. These detrimental effects of delaying treatment until FIB4 >3.25 were due to a reduction in the likelihood that treated patients would achieve viral load suppression and a reduced impact of viral load suppression on morbidity. Conclusions: Delaying treatment until after a patient’s FIB4 level exceeds 3.25 has a clear detrimental effect on treatment effectiveness
O004 ON-TREATMENT VIROLOGIC RESPONSE AND TOLERABILITY OF SIMEPREVIR, DACLATASVIR AND RIBAVIRIN IN PATIENTS WITH RECURRENT HEPATITIS C VIRUS GENOTYPE 1b INFECTION AFTER ORTHOTOPIC LIVER TRANSPLANTATION (OLT): INTERIM DATA FROM THE PHASE II SATURN STUDY X. Forns1 , M. Berenguer2 , K. Herzer3 , M. Sterneck4 , M.F. Donato5 , P. Andreone6 , S. Fagiuoli7 , T. Cieciura8 , M. Durlik8 , J.L. Calleja9 , Z. Marino ˜ 1 , A. Simion10 , U. Shukla11 , T. Verbinnen10 , O. Lenz10 , S. Ouwerkerk-Mahadevan12 , M. Peeters10 , R. Kalmeijer11 , J. Witek11 . 1 Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, 2 Department of Digestive Diseases, Hepatology and Liver Transplantation Unit, La Fe University Hospital and CIBEREHD, Valencia, Spain; 3 Department for Gastroenterology and Hepatology, University Hospital Essen, Essen, 4 Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 5 Division of Digestive Diseases, IRCCS Maggiore Hospital, Milan, 6 Department of Medical and Surgical Sciences, University of Bologna, Bologna, 7 Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy; 8 Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland; 9 Department of Gastroenterology and Hepatology, University Hospital Puerta de Hierro Mahadahonda, Madrid, Spain; 10 Janssen Infectious Diseases BVBA, Beerse, Belgium; 11 Janssen Research & Development LLC, Titusville, NJ, United States; 12 Janssen Research and Development, Beerse, Belgium E-mail: [email protected] Background and Aims: Simeprevir (SMV) and daclatasvir (DCV) are approved for the treatment of hepatitis C virus (HCV) infection in the non-transplant setting. SMV is a NS3/4A protease inhibitor and DCV is a NS5A replication complex inhibitor. The combination of SMV+DCV±ribavirin (RBV) has been previously evaluated in treatment-naïve and prior null responder patients (pts; LEAGUE-1). SATURN is an ongoing open-label Phase II study, investigating SMV+DCV+RBV in pts with recurrent HCV genotype 1b infection after orthotopic liver transplantation (OLT). Virologic response and tolerability results are presented from a pre-planned interim analysis. Methods: Post-OLT treatment-naïve or -experienced (prior relapser, partial or null responder to peginterferon±RBV) adults on stable immunosuppressive therapy following OLT were included. Part 1 (P1) included pts with METAVIR score F1–F2 on cyclosporine (CsA) or tacrolimus (TAC). Part 2 (P2) included F1–F4 pts on TAC. Pts received SMV (150 mg once daily [QD]), DCV (60 mg QD) and RBV (1–1.2 g/day) for 24 weeks. At the time of analysis, all P1 pts had reached end of treatment (EOT) and in P2, Week 4 of treatment (or early discontinuation). Analyses were based on the intent-to-treat population. Results: A total of 21 (P1) and 14 (P2) pts were included (P1/P2: female, 33%/43%; median age, 63.0 years [y]/59.5 y; mean time since transplantation, 3.98 y/5.36 y; median baseline HCV RNA 6.9 log10 /6.9 log10 IU/mL; METAVIR F3/F4, 0%/57%). P1 CsA pts had ~6-fold higher SMV plasma concentrations leading to SMV dose adjustment and exclusion of CsA pts from P2. On-treatment virologic response is shown in the Table. In P1, 91% of pts had HCV RNA
