studies

754A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Phillip S. Pang - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
Steven J. Knox - Employment: Gilead Sciences
John G. McHutchison - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Masao Omata - Advisory Committees or Review Panels: Boehringer Ingelheim;
Speaking and Teaching: Otsuka Pharmaceutical, Bayer
The following authors have nothing to disclose: Masashi Mizokami, Kwang-Hyub
Han, Jia-Horng Kao
1106
Efficacy, Change in MELD Score, and Safety by Baseline
MELD Score in Patients With Compensated Cirrhosis
Receiving Ombitasvir/Paritaprevir/r and Dasabuvir Plus
Ribavirin in the Phase 3 TURQUOISE-II Trial
Ira M. Jacobson 1 , Tania M. Welzel 2 , Hugo E. Vargas 3 , Marcos
C. Pedrosa 4 , Norah Terrault 5 , Douglas Dieterich 6 , Fredric D.
Gordon 7 , Kris V. Kowdley 8 , Guy Neff 4 , Ran Liu 4 , Juan-Carlos
Lopez-Talavera 4 , Stefan Zeuzem 2 ; 1 Weill Cornell Medical College,
New York, NY; 2 J.W. Goethe University, Frankfurt, Germany;
3 Mayo Clinic Arizona, Phoenix, AZ; 4 AbbVie Inc., North Chicago,
IL; 5 University of California San Francisco, San Francisco,
CA; 6 Mount Sinai School of Medicine, Icahn School of Medicine
at Mount Sinai, New York, NY; 7 Lahey Hospital & Medical Center,
Burlington, MA; 8 Liver Care Network, Swedish Medical Center,
Seattle, WA
Purpose: Curing HCV infection reduces the risk of complications
such as liver decompensation and hepatocellular carcinoma.
The 3 direct-acting antiviral (3D) regimens of co-formulated
ombitasvir/paritaprevir/r (paritaprevir identified by AbbVie
and Enanta, dosed with ritonavir [r]) and dasabuvir +/- ribavirin
(RBV) have achieved high SVR12 rates among adults with
chronic genotype 1 HCV, including those with compensated
cirrhosis. Model for end-stage liver disease (MELD) scores
assess liver disease severity. In this analysis, we evaluated
efficacy and safety of 3D+RBV and changes in MELD score by
baseline MELD score in the phase 3 TURQUOISE-II trial. Methods:
Treatment-naïve or peginterferon/RBV treatment-experienced
patients with compensated cirrhosis were randomized
to receive either 12 or 24 weeks of 3D+RBV in TURQUOISE-II.
SVR12, change in MELD score, and adverse event rates are
reported for subgroups of patients with baseline MELD scores
of 6-9, 10-13, and >14. Results: 380 patients were randomized
and received either 12 or 24 weeks of study drug. SVR12
rates were 94.2% (322/342), 93.9% (31/33), and 80.0%
(4/5) in patients with baseline MELD scores of 6-9, 10-13, and
>14, respectively. The 1 patient with MELD >14 not achieving
SVR12 discontinued study drug prematurely. Changes in MELD
score in patients who achieved SVR12 is in the table. Rate of
serious adverse events was 5.3% (18/342), 6.1% (2/33),
and 0% (0/5) for the 6-9, 10-13, and >14 subgroups, respectively.
Rate of discontinuation due to adverse events was 2.0%
(7/342), 0% (0/33), and 20.0% (1/5) for the 6-9, 10-13, and
>14 subgroups, respectively. Conclusions: In TURQUOISE-II,
3D+RBV demonstrated high SVR12 rates and favorable safety
in cirrhotic patients regardless of baseline MELD score. While
this analysis is limited by the small number of patients, the data
suggest improvements in MELD scores in patients with higher
baseline MELD scores.
Table. Changes in MELD score for patients who achieved SVR12.
*PTW48 data were not available for all patients who achieved
SVR12. Only data for those patients with data at PTW48 is
shown. PTW, post-treatment week.
Disclosures:
Ira M. Jacobson - Consulting: AbbVie, Achillion, Alnylam, Bristol Myers Squibb,
Enanta, Gilead, Janssen, Merck; Grant/Research Support: AbbVie, Bristol Myers
Squibb, Gilead, Janssen, Merck, Tobira; Speaking and Teaching: AbbVie, Bristol
Myers Squibb, Gilead, Janssen
Tania M. Welzel - Advisory Committees or Review Panels: Novartis, Janssen,
Gilead, Abbvie, Boehringer-Ingelheim+, BMS
Norah Terrault - Advisory Committees or Review Panels: Eisai, Biotest; Consulting:
BMS, Merck, Achillion; Grant/Research Support: Eisai, Biotest, Vertex,
Gilead, AbbVie, Novartis, Merck
Douglas Dieterich - Advisory Committees or Review Panels: Gilead, BMS, Abbvie,
Janssen, Merck, Achillion
Fredric D. Gordon - Advisory Committees or Review Panels: Gilead, AbbVie;
Grant/Research Support: BMS, Vertex, Gilead, AbbVie
Kris V. Kowdley - Advisory Committees or Review Panels: Achillion, BMS, Evidera,
Gilead, Merck, Novartis, Trio Health, Abbvie; Grant/Research Support:
Evidera, Gilead, Immuron, Intercept, Tobira; Speaking and Teaching: Abbvie,
Gilead
Ran Liu - Employment: Abbvie
Juan-Carlos Lopez-Talavera - Employment: Abbvie; Stock Shareholder: BMS
Stefan Zeuzem - Consulting: Abbvie, Bristol-Myers Squibb Co., Gilead, Merck
& Co., Janssen
The following authors have nothing to disclose: Hugo E. Vargas, Marcos C.
Pedrosa, Guy Neff
1107
Efficacy and safety of ombitasvir/paritaprevir/r and
dasabuvir +/- ribavirin in HCV genotype 1-infected
patients with a history of bleeding disorders: Results
from phase 3 trials
Giustino Parruti 1 , Guilherme Macedo 2 , Axel Baumgarten 3 ,
Frederik Nevens 4 , Jordan J. Feld 5 , Christophe Hezode 6 , Lois
M. Larsen 7 , Nancy Shulman 7 , Regis A. Vilchez 7 , Heiner Wedemeyer
8 ; 1 Ospedale Civile Spirito Santo, Pescara, Italy; 2 Centro
Hospitalar de São João, Porto, Portugal; 3 Medical Center for Infectious
Diseases, Berlin, Germany; 4 University Hospitals KU, Leuven,
Belgium; 5 Toronto Centre for Liver Disease, University of Toronto,
Toronto, ON, Canada; 6 Henri Mondor University Hospital, AP-HP,
Université Paris-Est, Créteil, France; 7 AbbVie Inc., North Chicago,
IL; 8 Medizinische Hochschule Hannover, Hannover, Germany
Background: HCV infection has been prevalent in patients with
bleeding disorders due to the high frequency of contamination
of blood-derived clotting factor products prior to the 1990s.
The 3 direct-acting antiviral (3D) regimens of co-formulated
ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, PTV identified
by AbbVie and Enanta) and dasabuvir (DSV) +/- ribavirin
(RBV) have achieved high SVR12 rates among adults with
chronic genotype 1 HCV including those with compensated
cirrhosis. In this analysis, we examined the efficacy and safety
of 3D+/-RBV in patients with a history of bleeding disorders in
phase 3 trials. Methods: Treatment-naïve or peginterferon/RBV
treatment-experienced, cirrhotic or non-cirrhotic HCV genotype
1-infected patients enrolled in phase 3 trials and received
3D+/-weight-based RBV. The efficacy (SVR12 rate) and safety
for patients with a history of bleeding disorders is reported.
Results: Thirty-five patients with a history of bleeding disorders
(29 of whom had hemophilia) were enrolled and received
active study drug (32 patients, 3D+RBV; 3 patients, 3D). Baseline
characteristics and efficacy results are in the table. Fifteen