studies

744A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Heiner Wedemeyer - Advisory Committees or Review Panels: Transgene, MSD,
Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK, Roche Diagnostics;
Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott, Roche Diagnostics;
Speaking and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead
Xavier Forns - Consulting: Jansen, Abbvie; Grant/Research Support: Jansen,
Gilead
Pietro Andreone - Advisory Committees or Review Panels: Janssen-Cilag, Gilead,
MSD/Schering-Plough, Abbvie; Speaking and Teaching: Gilead, BMS
Massimo Colombo - Advisory Committees or Review Panels: BRISTOL-MEY-
ERS-SQUIBB, SCHERING-PLOUGH, ROCHE, GILEAD, BRISTOL-MEYERS-SQUIBB,
SCHERING-PLOUGH, ROCHE, GILEAD, Janssen Cilag, Achillion; Grant/
Research Support: BRISTOL-MEYERS-SQUIBB, ROCHE, GILEAD, BRISTOL-MEY-
ERS-SQUIBB, ROCHE, GILEAD; Speaking and Teaching: Glaxo Smith-Kline,
BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH, ROCHE, NOVARTIS, GILEAD,
VERTEX, Glaxo Smith-Kline, BRISTOL-MEYERS-SQUIBB, SCHERING-PLOUGH,
ROCHE, NOVARTIS, GILEAD, VERTEX, Sanofi
David Bernstein - Advisory Committees or Review Panels: Gilead; Consulting:
Abbvie, BMS, Merck, Janssen; Grant/Research Support: Gilead, Abbvie, BMS,
Merck, Janssen, Genentech; Speaking and Teaching: Abbvie, BMS, Merck,
Gilead
Fred Poordad - Advisory Committees or Review Panels: Abbott/Abbvie, Achillion,
BMS, Inhibitex, Boeheringer Ingelheim, Pfizer, Genentech, Idenix, Gilead,
Merck, Vertex, Salix, Janssen, Novartis; Grant/Research Support: Abbvie,
Anadys, Achillion, BMS, Boehringer Ingelheim, Genentech, Idenix, Gilead,
Merck, Pharmassett, Vertex, Salix, Tibotec/Janssen, Novartis
Christophe Hezode - Speaking and Teaching: Roche, BMS, MSD, Janssen, abbvie,
Gilead
Thomas Podsadecki - Employment: AbbVie; Stock Shareholder: AbbVie
Wangang Xie - Employment: AbbVie
Tami Pilot-Matias - Employment: AbbVie; Stock Shareholder: AbbVie
Regis A. Vilchez - Employment: AbbVie Inc.
John M. Vierling - Advisory Committees or Review Panels: Abbvie, Bristol-Meyers-Squibb,
Gilead, Hyperion, Intercept, Janssen, Novartis, Merck, Sundise,
HepQuant, Salix, Immuron, Exalenz, Chronic Liver Disease Foundation; Board
Membership: Clinical Research Centers of America, LLC; Grant/Research Support:
Abbvie, Bristol-Meyers-Squibb, Eisai, Gilead, Hyperion, Intercept, Janssen,
Novartis, Merck, Sundise, Ocera, Mochida, Immuron, Exalenz, Conatus; Speaking
and Teaching: GALA, Chronic Liver Disease Foundation, ViralEd, Chronic
Liver Disease Foundation, Clinical Care Options
in lifetime risks of developing advanced liver disease (i.e. CC,
DCC or HCC) and an 80% reduction in risks of LrD, regardless
of treatment history or cirrhosis status. The lifetime risks of
liver morbidity and mortality are also substantially lower in the
overall coinfected patients treated with 3D±R than those treated
with SOF+PR or SOF+R. In the naïve non-cirrhotic coinfected
patients, treatment with 3D±R offers comparable reductions
in lifetime risks of liver morbidity and mortality compared to
SOF+LDV. Conclusion Compared with former or other current
standards of care for treating GT1 HCV and HIV coinfected
patients in the US, 3D±R offers favorable or comparable reductions
in lifetime risks of liver morbidity and mortality.
Lifetime risks of liver morbidity and mortality in GT1 HCV and HIV
coinfected patients
* Clinical trial data not available
Disclosures:
Sammy Saab - Advisory Committees or Review Panels: BMS, Gilead, Merck,
Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead,
Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion,
Johnson and Johnson, BMS, Gilead
Suchin Virabhak - Consulting: AbbVie
Scott J. Johnson - Consulting: AbbVie; Employment: Medicus Economics
Hélène Parisé - Consulting: MedicusEconomics LLC, AbbVie ; Employment: Statlog
Consulting Inc
Yuri Sanchez - Employment: AbbVie; Stock Shareholder: AbbVie
Timothy R. Juday - Employment: AbbVie; Stock Shareholder: AbbVie
The following authors have nothing to disclose: Alice Wang
1087
Lifetime risks of liver morbidity and mortality in patients
with chronic genotype (GT) 1 hepatitis C virus (HCV)
and HIV coinfection treated with 3D±R (ombitasvir/
paritaprevir/ ritonavir, dasabuvir ± ribavirin) vs other
standards of care in the US
Sammy Saab 2 , Suchin Virabhak 3 , Scott J. Johnson 3 , Hélène
Parisé 3 , Yuri Sanchez 1 , Alice Wang 1 , Timothy R. Juday 1 ; 1 HEOR,
AbbVie, Mettawa, ID; 2 Pfleger Liver Institute, UCLA, Los Angeles,
CA; 3 Medicus Economics Inc., Boston, MA
Objective This study evaluated the lifetime risks of liver morbidity
and mortality in patients with GT1 HCV and HIV coinfection
treated with 3D±R for 12 or 24 weeks compared to other standards
of care in the United States (US): sofosbuvir plus peg-interferon
and ribavirin for 12 weeks (SOF+PR) and SOF+R for
24 weeks in the overall coinfected population, and sofosbuvir
plus ledipasvir for 12 weeks (SOF+LDV) in the treatment-naïve
non-cirrhotic population. Methods A Markov model based on
the natural history of liver disease progression estimated the
risks of liver-related morbidity and mortality over a lifetime
horizon for a cohort of patients with GT1 HCV and HIV coinfection.
Baseline population characteristics and efficacy data
were obtained from published clinical trials. Lifetime risks of
compensated cirrhosis (CC), decompensated cirrhosis (DCC),
hepatocellular carcinoma (HCC) and liver-related death (LrD)
were analyzed. Treatment strategies included ‘no treatment’
(NT), as well as regimens that have been studied in Phase II or
III clinical trials of coinfected patients, and either recommended
by the latest guidelines or approved by the Food and Drug
Administration. Results Compared to untreated GT1 HCV and
HIV coinfected patients, 3D±R offers at least a 59% reduction
1088
Effect of Chronic Kidney Disease on the Pharmacokinetics
of Ombitasvir, Paritaprevir, Ritonavir and Dasabuvir
in Subjects with HCV Genotype 1 Infection
Diana L. Shuster, Rajeev Menon, Daniel E. Cohen, Amit Khatri;
AbbVie, North Chicago, IL
Background and Objective: The all-oral interferon-free, 3
direct acting antiviral (3-DAA) regimen of ombitasvir (OBV)
(NS5A inhibitor) + paritaprevir (NS3/4A protease inhibitor
identified by AbbVie and Enanta), coadministered with ritonavir,
a pharmacokinetic enhancer (PTV/r), + dasabuvir (DSV)
(NS5B non-nucleoside polymerase inhibitor) ± ribavirin (RBV)
is being evaluated in HCV genotype (GT) 1-infected subjects
with chronic kidney disease (CKD). No meaningful alterations
in exposures were seen when the 3 DAAs were administered
to HCV-uninfected subjects with renal impairment. The present
analysis examines the effect of CKD Stage 4 and Stage
5 on the pharmacokinetics of OBV, PTV/r and DSV in HCV
GT1-infected subjects. Methods: Pharmacokinetic data from
a Phase 2 study (N=38) in subjects with normal or mild renal
impairment (subjects “without kidney disease”) were combined
with preliminary data from a Phase 3b study in subjects with
CKD Stage 4 (N=5) or Stage 5 on hemodialysis (N=14). In
both studies subjects received OBV/PTV/r 25/150/100 mg
QD and DSV 250 mg BID ± RBV for 12 weeks. Pharmacokinetic
parameters and steady-state exposures of the 3-DAA
regimen were estimated using population pharmacokinetic
models. Results: CKD was not a significant covariate in the
population pharmacokinetic analyses, and the safety profile
of the 3 DAAs was similar in subjects with or without CKD.
PTV and DSV exposures were comparable (