studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1191A
2015
Safety and Efficacy of GS-4774 in Patients with Chronic
Hepatitis B on Oral Antiviral Therapy
Anna S. Lok 1 , Calvin Q. Pan 2 , Steven-Huy B. Han 3 , Huy N.
Trinh 4 , Jeffrey Fessel 5 , Tim Rodell 6 , Benedetta Massetto 7 , Anh-Hoa
Nguyen 7 , Anuj Gaggar 7 , Mani Subramanian 7 , John G. McHutchison
7 , Carlo Ferrari 8 , Hannah Lee 9 , Stuart C. Gordon 10 , Edward
J. Gane 11 ; 1 University of Michigan Health System, Ann Arbor,
MI; 2 Medical Procare, PLLC, Flushing, NY; 3 Ronald Reagan UCLA
Medical Center, Los Angeles, CA; 4 San Jose Gastroenterology,
San Jose, CA; 5 Kaiser Permanente, San Francisco, CA; 6 Globeimmune,
Louisville, CO; 7 Gilead Sciences, Inc., Foster City, CA; 8 University
of Parma, Parma, Italy; 9 Tufts Medical Center, Boston, MA;
10 Henry Ford Hospital, Detroit, MI; 11 Auckland General Hospital,
Auckland, New Zealand
Background: Chronic HBV infection is associated with a
dysfunctional T-cell response. GS-4774 is a heat-inactivated
yeast-based therapeutic T-cell vaccine expressing a recombinant
protein containing HBV core, surface, and X proteins to
elicit an HBV-specific T-cell response. This Phase 2 study evaluated
GS-4774 in virally-suppressed chronic hepatitis B (CHB)
patients. Methods: In this multicenter study, 178 non-cirrhotic
patients with CHB were enrolled. All patients were virally suppressed
on an oral antiviral (OAV) for >1 year. Patients were
randomized to continue OAV alone or to continue OAV and
receive GS-4774 every 4 weeks for 6 doses at either 2 yeast
units (YU), 10 YU, or 40 YU [1 YU=10^7 yeast cells]. The
primary endpoint was decline from baseline in quantitative
serum HBsAg (Abbot Architect Assay) at Week 24. Safety
assessments include monitoring of injection site reactions,
hepatic flares, and virologic breakthrough. Results: Baseline
demographics were similar across all groups. The mean age
of patients was 45 to 50 years and 62-74% were men. The
majority (68-80%) of patients was Asian, 24-26% were HBeAg
positive, and the mean duration of prior OAV treatment was
4.4-4.8 years. Grade 3 or 4 adverse events (AEs) occurred in
30%
reductions in HBsAg (observed variability in the OAV arm)
at Week 48 (Panel B) at all timepoints. No patients achieved
HBsAg loss. Five of 32 (16%) HBeAg positive patients treated
with GS-4774 experienced HBeAg loss with 4 having HBeAg
seroconversion. No virologic breakthrough was observed. Conclusions:
GS-4774 was safe and well-tolerated in CHB patients
with no patients achieving HBsAg loss during the study. Modest
reductions in HBsAg were observed in some patients treated
with GS-4774.
Disclosures:
Anna S. Lok - Advisory Committees or Review Panels: Gilead, MYR, Tekmira;
Consulting: GSK, Merck; Grant/Research Support: AbbVie, BMS, Gilead, Idenix
Calvin Q. Pan - Advisory Committees or Review Panels: Gilead; Consulting:
BMS, Gilead, Abbvie, Janssen ; Grant/Research Support: BMS, Gilead, Merck;
Speaking and Teaching: BMS, Gilead, Abbvie
Steven-Huy B. Han - Grant/Research Support: Bristol Myers Squibb, Gilead
Huy N. Trinh - Advisory Committees or Review Panels: BMS, Gilead; Grant/
Research Support: BMS, Gilead; Speaking and Teaching: BMS, Gilead; Stock
Shareholder: Gilead
Jeffrey Fessel - Grant/Research Support: gilead, bms, abbvie, gsk, johnson &
johnson
Benedetta Massetto - Employment: Gilead Sciences, Inc.; Stock Shareholder:
Gilead Sciences, Inc
Anuj Gaggar - Employment: Gilead Sciences, Inc.
Mani Subramanian - Employment: Gilead Sciences
John G. McHutchison - Employment: Gilead Sciences; Stock Shareholder: Gilead
Sciences
Carlo Ferrari - Advisory Committees or Review Panels: Gilead, Roche, Abbvie,
BMS, Merck, Arrowhead; Grant/Research Support: Gilead, Roche, Janssen
Stuart C. Gordon - Advisory Committees or Review Panels: Janssen; Consulting:
Merck, Gilead, BMS, CVS Caremark, Amgen, AbbVie; Grant/Research Support:
Merck, Gilead, AbbVie, Intercept Pharmaceuticals, Exalenz Sciences, Inc., BMS
Edward J. Gane - Advisory Committees or Review Panels: Novira, AbbVie, Janssen,
Gilead Sciences, Janssen Cilag, Achillion, Merck, Tekmira; Speaking and
Teaching: AbbVie, Gilead Sciences, Merck
The following authors have nothing to disclose: Tim Rodell, Anh-Hoa Nguyen,
Hannah Lee
2016
Entecavir and Tenofovir More Effectively Reduce the
Recurrence of Hepatitis B Virus-related Hepatocellular
Carcinoma after Curative Treatment than Low-potent
Antivirals
Hongkeun Ahn 1 , Jeong-Hoon Lee 1 , YOUNG CHANG 1 , Joon Yeul
Nam 1 , Hyeki Cho 1 , Young Youn Cho 1 , Minjong Lee 1 , Jeong-Ju
Yoo 1 , Yuri Cho 1 , Donghyeon Lee 1 , Eun Ju Cho 1 , Su Jong Yu 1 ,
Yoon Jun Kim 1 , Jung-Hwan Yoon 1 , June Sung Lee 2 ; 1 Department of
Internal Medicine and Liver Research Institute, Seoul National University
Hospital, Seoul, Korea (the Republic of); 2 Internal Medicine,
Inje University, Ilsan Paik Hospital, Goyang, Korea (the Republic
of)
Backgroud and Aim: The effect of antiviral potency of nucleos(t)ide
analogues (NAs) on the recurrence of hepatocellular
carcinoma (HCC) in chronic hepatitis B (CHB) patients has
not been well investigated. This study aimed to evaluate the
association of the potency of antivirals and the risk of hepatitis
B virus (HBV)-related HCC recurrence after potentially curative
treatment. Methods: We performed a retrospective analysis of
data from 473 consecutive hepatitis B virus (HBV)-related HCC
patients treated with radio-frequency ablation (RFA, n=261)
or resection (n=212). According to the potency of antiviral
treatments, total population was divided into three groups:
group A (no antiviral treatment, n=224), group B (low-potent
NA: telbivudine, adefovir, clevudine, and lamivudine; n=76),
group C (high-potent NA: entecavir [ETV] and tenofovir disoproxil
fumarate [TDF]; n=173). Recurrence-free survival (RFS)
in three groups were analyzed by Kaplan-Meier curve analysis
and Cox proportional hazards model. Results: The median
follow-up duration was 56.9 months. The median RFS was
38.3, 43.6, and 92.9 months in group A, group B, and group
C, respectively (P=0.012 by log-rank test). In multivariate
analysis, group C had significantly prolonged RFS (hazard
ratio [HR]=0.55, 95% confidence interval [CI]=0.42–0.74;
P