studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 337A
Three hundred forty-one patients were on lamivudine, 60 were
on adefovir, 188 were on entecavir, 467 were on tenofovir,
and 32 were on combination therapies. ROC analysis for the
predictive values of HCC scores showed that AUROC values
were 0.804 for CU-HCC, 0.809 for REACH-B and 0.882 for
GAG-HCC. These values were similar in patients without therapy
and with entecavir and tenofovir therapies as in the literature.
The most predictive GAG-HCC score had sensitivity of
97.3% and negative predictive value of 99.9%. Conclusion:
In this large cohort of Caucasian HBV patients, all of these
scores had good predictive values for HCC development both
in patients on treatment and in patients who did not receive
antiviral treatment.
Disclosures:
Ulus S. Akarca - Advisory Committees or Review Panels: GILEAD, BMS, MSD,
AbbVie
The following authors have nothing to disclose: Fulya Gunsar, Ilker Turan, Galip
Ersoz, Zeki Karasu, Omer Ozutemiz
247
High Rates of SVR in Treatment-Experienced Patients
with Genotype 1 HCV Infection and Cirrhosis After
Treatment with Ledipasvir/Sofosbuvir and Vedroprevir
with or Without Ribavirin for 8 weeks
Eric Lawitz 1 , Fred Poordad 1 , Robert H. Hyland 2 , Lin Liu 2 , Hadas S.
Dvory 2 , Phillip S. Pang 2 , Diana M. Brainard 2 , Julio A. Gutierrez 1 ;
1 Texas Liver Institute, San Antonio, TX; 2 Gilead Sciences, Inc, Foster
City, CA
Background: Ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination
± ribavirin (RBV) for 12 weeks in patients with HCV
genotype 1 and cirrhosis is safe and effective. We previously
showed that LDV/SOF plus the non-nucleotide NS5B inhibitor
GS-9669 for 8 weeks resulted in 82-91% SVR12 in patients
with cirrhosis and genotype 1 HCV infection. In the current
study, we evaluated the safety and efficacy of 8 weeks of LDV/
SOF plus the HCV NS3 protease inhibitor vedroprevir (VDV,
GS-9451) ± RBV in genotype 1 HCV-infected patients with
cirrhosis. Methods: Patients, previously treated with pegylated
interferon+RBV, with compensated cirrhosis and chronic HCV
genotype 1 infection were randomized equally to receive LDV/
SOF+VDV or LDV/SOF+VDV+RBV for 8 weeks. Deep sequencing
was performed for all patients who didn’t achieved SVR12.
Results: 46 patients were randomized and treated. The majority
were male (65%), Caucasian (96%), and had HCV genotype
1a (70%), and were IL28B non-CC (87%). The median
HCV RNA was 6.0 log 10
IU/ml. Rates of on-treatment Week 4
viral suppression, SVR12, and relapse are shown in the table.
NS5A RAVs were detected in all 3 subjects who relapsed.
LDV/SOF+VDV±RBV was safe and well tolerated. There were
no SAEs. One patient was lost to follow up having completed
only 4 weeks of therapy. There were no discontinuations due
to adverse events. Adverse events were generally mild, and
Grade 3/4 laboratory abnormalities were infrequent. The most
frequent adverse events were headache, rash, and sinusitis.
Conclusions: Ledipasvir/sofosbuvir +VDV for 8 weeks achieved
high SVR rates in genotype 1 HCV-infected treatment-experienced
patients with cirrhosis irrespective of the addition of RBV.
Both regimens were safe and well tolerated.
Disclosures:
Eric Lawitz - Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals,
Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Merck
& Co, Novartis, Gilead; Grant/Research Support: AbbVie, Achillion Pharmaceuticals,
Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmith-
Kline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co,
Novartis, Nitto Denko, Theravance, Salix, Enanta; Speaking and Teaching: Gilead,
Janssen, AbbVie, Bristol Meyers Squibb
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
Robert H. Hyland - Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead
Sciences, Inc
Lin Liu - Employment: Gilead Sciences, Inc.
Phillip S. Pang - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
Diana M. Brainard - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
The following authors have nothing to disclose: Hadas S. Dvory, Julio A. Gutierrez
248
High SVR4 Rates Achieved With the Next Generation
NS3/4A Protease Inhibitor ABT-493 and NS5A Inhibitor
ABT-530 in Non-Cirrhotic Treatment-Naïve and Treatment-Experienced
Patients With HCV Genotype 3 Infection
(SURVEYOR-2)
Paul Y. Kwo 1 , Michael Bennett 2,3 , Stanley Wang 4 , Hugo E.
Vargas 5 , David L. Wyles 6 , J. Scott Overcash 7 , Peter J. Ruane 8 ,
Benedict Maliakkal 9 , Asma Siddique 10 , Bal R. Bhandari 11 , Fred
Poordad 12 , Ran Liu 4 , Chih-Wei Lin 4 , Teresa Ng 4 , Federico J.
Mensa 4 , Jens Kort 4 ; 1 Division of Gastroenterology, Indiana University
Medical Center, Indianapolis, IN; 2 San Diego Digestive
Disease Consultants, Inc., San Diego, CA; 3 Medical Associates
Research Group, Inc., San Diego, CA; 4 AbbVie Inc., North Chicago,
IL; 5 Mayo Clinic, Phoenix, AZ; 6 University of California San
Diego, La Jolla, CA; 7 eStudySite, San Diego, CA; 8 Ruane Medical
& Liver Health Institute, Los Angeles, CA; 9 University of Rochester
Medical Center, Rochester, NY; 10 Virginia Mason Hospital and
Medical Center, Seattle, WA; 11 Gastroenterology & Nutritional
Medical Services, Bastrop, LA; 12 Texas Liver Institute, University of
Texas Health Science Center, San Antonio, TX
Background: The next generation HCV direct acting antivirals
(DAAs) ABT-493, an NS3/4A protease inhibitor identified by
AbbVie and Enanta, and ABT-530, an NS5A inhibitor, are
characterized by potent pan-genotypic in vitro antiviral activity
and a high barrier to resistance selection with retention
of activity against key known resistance-associated variants.
ABT-493 and ABT-530 each provided a mean 4 log 10
IU/mL
decline from baseline in HCV plasma viral load after 3 day
monotherapy in genotype (GT) 1-infected subjects and have
comparable in vitro antiviral potency against GT3a. Purpose:
To evaluate the efficacy and safety of ABT-493 and ABT-530
with or without ribavirin (RBV) in non-cirrhotic GT3-infected
treatment-naïve (TN) and pegylated interferon/RBV (pegIFN/
RBV) treatment experienced (TE) subjects Methods: Subjects
received 12 weeks of ABT-493 300 mg+ABT-530 120 mg
(Arm D), ABT-493 200 mg+ABT-530 120 mg (Arm E), ABT-
493 200 mg+ABT-530 120 mg+RBV (Arm F), or ABT-493 200
mg+ABT-530 40 mg (Arm G). DAAs were dosed once daily;
weight-based RBV (1000 or 1200 mg) was dosed twice daily.
The primary efficacy endpoint is sustained virologic response
12 weeks after the last dose of study drug (SVR12); we present
post-treatment week 4 data (SVR4) here. Safety was evaluated
by monitoring adverse events (AEs), laboratory tests, and vital
signs. Results: 120 GT3-infected subjects were treated in Arms