studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 571A
Dennis Wolford - Employment: Merck Sharpe & Dohme Corp., a subsidiary of
Merck and Co., Inc.; Stock Shareholder: Merck Sharpe & Dohme Corp., a subsidiary
of Merck and Co., Inc.
William L. Marshall - Employment: Merck
Marian Iwamoto - Employment: Merck Sharp & Dohme Corp.
Joan R. Butterton - Employment: Merck Sharp & Dohme Corp.; Stock Shareholder:
Merck Sharp & Dohme Corp.
The following authors have nothing to disclose: Katherine M. Dunnington, Nadia
Cardillo Marricco, Michael Gartner, Dennis Swearingen, John Brejda, Angela
O. Choi
726
Integrated Safety Analysis of Daclatasvir Plus Sofosbuvir,
With or Without Ribavirin, in Patients With HCV
Genotype 3 Infection
David Bernstein 1 , Charles S. Landis 2 , Eric Lawitz 3 , Anne Luetkemeyer
4 , Melissa Harris 5 , Rafia Bhore 5 , Eugene S. Swenson 6 ,
Peter Ackerman 6 , Khurram Rana 6 , Douglas Dieterich 7 ; 1 Hofstra
North Shore-Long Island Jewish School of Medicine, Manhasset,
NY; 2 University of Washington School of Medicine, Seattle, WA;
3 Texas Liver Institute, University of Texas Health Science Center,
San Antonio, TX; 4 University of California and San Francisco General
Hospital, San Francisco, CA; 5 Bristol-Myers Squibb, Princeton,
NJ; 6 Bristol-Myers Squibb, Wallingford, CT; 7 Icahn School of Medicine
at Mount Sinai, New York, NY
Background: SVR12 rates of up to 98% have been achieved
in the three phase 3 ALLY studies with the pangenotypic combination
of daclatasvir (DCV) plus sofosbuvir (SOF), with or
without ribavirin (RBV). In patients with genotype (GT)3 infection
enrolled in these studies, SVR12 rates were 88–100%. The
safety profile of DCV+SOF±RBV in patients with GT3 infection
was evaluated using integrated data from the ALLY studies.
Methods: Integrated data were derived from 182 GT3-infected
patients enrolled in ALLY-1 (advanced cirrhosis or post-liver
transplant recurrence, N=17), ALLY-2 (HIV-HCV coinfection,
N=13), and ALLY-3 (GT3 infection, N=152). Patients were
treated with DCV 60mg (dose-adjusted for concomitant antiretroviral
therapy in HIV coinfected patients) +SOF 400mg
for 8 (ALLY-2) or 12 weeks (ALLY-2, ALLY-3) or with DCV+-
SOF+RBV for 12 weeks (ALLY-1). Integrated safety data were
analyzed for on-treatment adverse events (AEs), serious AEs
(SAEs), AE-related discontinuations, and grade 3/4 AEs and
lab abnormalities. Results: Patients were 64% male, 91%
white, and 64% HCV treatment-naive; the median age was
55 years and 21% had cirrhosis. In this cohort, there were
no treatment-related SAEs or deaths. There were 7 grade 3/4
AEs and 16 grade 3/4 lab abnormalities. Four AEs led to
discontinuation of study drug (all treatment-related): 3 events
were associated with RBV and led to discontinuation of only
RBV in patients with advanced cirrhosis; 1 event (headache)
in a liver transplant recipient led to discontinuation of all HCV
therapy after 4 weeks, but SVR12 was still achieved. Overall,
the most common AEs (any grade) in the ALLY studies
were fatigue (19%), headache (17%), and nausea (12%). As
expected, safety events were more frequent in patients with
advanced cirrhosis that received RBV; however, none of these
patients required discontinuation of all study therapies and
5/6 achieved SVR12. Conclusions: Safety events with DCV+-
SOF±RBV were uncommon in patients with HCV GT3 infection.
HIV coinfection had no notable impact on safety parameters;
events were more frequent in patients with advanced cirrhosis
that received RBV, but had minimal impact on SVR12. These
results support the use of DCV+SOF±RBV therapy in a broad
spectrum of patients with GT3 infection.
Disclosures:
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
Charles S. Landis - Grant/Research Support: Gilead, Abbvie, BMS
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
Anne Luetkemeyer - Grant/Research Support: Gilead, Abbvie, Pfizer, Bristol
Myers Squibb, Merck
Melissa Harris - Employment: Bristol-Myers Squibb
Eugene S. Swenson - Employment: Bristol-Myers Squibb
Peter Ackerman - Employment: Bristol-Myers, Squibb
Khurram Rana - Employment: Bristol-Myers Squibb
Douglas Dieterich - Advisory Committees or Review Panels: Gilead, BMS, Abbvie,
Janssen, Merck, Achillion
The following authors have nothing to disclose: Rafia Bhore
727
Projected Long-Term Impact of Grazoprevir (GZR,
MK-5172)/Elbasvir (EBR, MK-8742) in Treatment-Naive
and Treatment-Experienced Patients with Hepatitis C
Virus Genotype 1 Infection and Chronic Kidney Disease
Shannon A. Ferrante, Elamin Elbasha, Wayne Greaves, Chizoba
Nwankwo; Merck & Co., Inc, North Wales, PA
Background: Hepatitis C virus (HCV) infection is an important
cause of morbidity, liver disease-related deaths from complications
of decompensated cirrhosis (DC) and hepatocellular
carcinoma (HCC), and cardiovascular mortality in chronic kidney
disease (CKD) patients in the United States. GZR (NS3/4A
protease inhibitor) and EBR (NS5A inhibitor) were recently
studied in C-SURFER, a phase 2/3 double-blind, placebo-control
trial in HCV genotype 1 patients with CKD4/5. Aims: To
translate short-term findings from the C-SURFER trial into longterm
predictions of the impact of GZR/EBR on incidence of liver-related
morbidity and mortality compared with no treatment
(NoTX) and pegylated interferon plus ribavirin (peg-IFN/RBV).
Methods: A computer-based mathematical model of the natural
history of chronic HCV genotype 1 infection and chronic
kidney and liver disease was developed to project lifetime
cumulative incidence of DC, HCC, liver-transplant (LT) and
liver-related death. Efficacy of GZR/EBR was obtained from
C-SURFER trial. In the pre-specified primary population, the
proportion of patients achieving sustained viral response 12
weeks after the completion of therapy was 0.99 (0.95–1.00).
Based on the results of a meta-analysis, we assumed an efficacy
of 0.60 (0.47–0.71) for peg-IFN/RBV. Data on baseline
characteristics of the simulated patients were obtained from
the National Health and Nutrition Examination Survey. Natural
history parameters were estimated from published studies.