studies

340A AASLD ABSTRACTS HEPATOLOGY, October, 2015
A, B, and C, respectively. Most AEs were mild, with the most
common DAA-related AEs being fatigue, nausea, headache,
and diarrhea. There were no serious DAA-related AEs. Typical
reductions in hemoglobin were observed in the RBV-containing
arm. Conclusions: ABT-493+ABT-530 with or without RBV for
12 weeks was highly effective and well tolerated, achieving
SVR4 rates of 96%–100% and no virologic failure to-date;
SVR12 data will be available at the time of the meeting. These
data warrant further study of this once daily RBV-free ABT-493/
ABT-530 combination in GT2 infection, including patients with
cirrhosis.
Disclosures:
David L. Wyles - Advisory Committees or Review Panels: Bristol Myers Squibb,
Janssen, Merck; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb,
AbbVie, Tacere
Mark S. Sulkowski - Advisory Committees or Review Panels: Merck, AbbVie,
Janssen, Gilead, BMS; Grant/Research Support: Merck, AbbVie, Janssen, Gilead,
BMS
Stanley Wang - Employment: AbbVie
Benedict Maliakkal - Speaking and Teaching: Valeant Pharma (Salix), Gilead,
AbbVie, Bristol Myers 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
Sandra S. Lovell - Employment: AbbVie
Chih-Wei Lin - Employment: Abbvie
Teresa Ng - Employment: AbbVie; Patent Held/Filed: AbbVie; Stock Shareholder:
AbbVie
Federico J. Mensa - Employment: Abbvie Inc.; Stock Shareholder: Abbvie Inc.
Jens Kort - Employment: AbbVie Inc.; Stock Shareholder: AbbVie Inc.
The following authors have nothing to disclose: Michael Bennett, Hugo E. Vargas,
J. Scott Overcash, Asma Siddique, Bal R. Bhandari
251
High Efficacy of Grazoprevir and Elbasvir With or Without
Ribavirin in 103 Treatment-Naive and Experienced
Patients With HCV Genotype 4 Infection: A Pooled Analysis
Tarik Asselah 1 , Hendrik W. Reesink 2 , Jan Gerstoft 3 , Victor de Ledinghen
4 , Paul J. Pockros 5 , Michael Robertson 6 , Peggy Hwang 6 ,
Bach-Yen T. Nguyen 6 , Janice Wahl 6 , Eliav Barr 6 , Rohit Talwani 6 ,
Lawrence Serfaty 7 ; 1 Hôpital Beaujon, Clichy, France; 2 Academical
Medical Center, Amsterdam, Netherlands; 3 Rigshospitalet, University
of Copenhagen, Copenhagen, Denmark; 4 CHU Bordeaux,
Pessac, France; 5 Scripps Clinic, La Jolla, CA; 6 Merck & Co., Inc.,
Kenilworth, NJ; 7 Saint-Antoine Hospital, Paris, France
Background: Genotype (GT) 4 accounts for around 15% of the
170 million HCV infections worldwide, with high prevalence
in Middle East and sub-Saharan Africa, but also increasing in
Europe. Data on the efficacy of direct acting antiviral regimens
in the GT4 population are limited. We evaluated the efficacy
of the protease inhibitor grazoprevir 100 mg (GZR) and NS5A
inhibitor elbasvir 50 mg (EBR), with and without (±) ribavirin
(RBV) in GT4 infected patients enrolled in the GZR/EBR
phase 2/3 clinical program. Methods: Two pooled datasets
were evaluated: (1) treatment-naive (TN) patients who received
12 weeks of GZR/EBR ± RBV and (2) treatment-experienced
(TE) patients, defined as those who had previously failed
peginterferon + RBV (PR) ± first-generation protease inhibitor
who received 12, 16, or 18 weeks of GZR/EBR ± RBV. TE
patients were further classified as failures due to prior relapse
or prior on-treatment virologic failure (OTF) (eg, null or partial
response; virologic breakthrough). Efficacy was defined as sustained
virologic response (HCV RNA < assay-specified lower
limit of quantification) 12 weeks after end of therapy (SVR12)
in the full analysis set (all patients who received at least 1 dose
of study drug). Results: Data from a total of 103 HCV-GT4 (47
GT4a, 47 GT4d, 9 GT4-other)–infected patients, 66 TN and
37 TE, including 17 cirrhotic patients, were analyzed. Overall
64/66 (97%) TN (including 6/6 cirrhotic patients) and 32/37
(86%) TE GT4 patients achieved SVR12. Among TE patients,
9/9 prior relapsers and 23/28 (82%) prior OTFs achieved
SVR12. Among TE cirrhotic patients, 13/17 (77%) including
3/3 prior relapsers and 4/4 treated with GZR/EBR+RBV for
16 weeks achieved SVR12. For prior OTFs, longer durations
and use of RBV increased the response rate. Additional stratification
of treatment responses according to regimen is included
in Table 1. Conclusion: A 12-week regimen of GZR/EBR was
highly effective among 103 GT4-infected TN and prior relapse
patients. A regimen of GZR/EBR + RBV for 16 weeks may
result in improved efficacy among prior OTF patients, although
sample size was small. Further studies among subpopulations
are needed.
Table 1
a Other: Non-SVR, but did not meet virologic failure criteria
Disclosures:
Tarik Asselah - Advisory Committees or Review Panels: AbbVie, Merck, Gilead,
BMS, Roche, Janssen
Hendrik W. Reesink - Consulting: Abbvie, Alnylam, BMS, Gilead, Janssen-Cilag,
Merck, PRA-International, Regulus, Replicor, Roche, R-Pharm; Grant/Research
Support: AbbVie, BMS, Boehringer Ingelheim, Gilead, Janssen-Cilag, Merck,
PRA-International, Regulus, Replicor, Roche
Victor de Ledinghen - Board Membership: Janssen, Gilead, BMS, Abbvie; Speaking
and Teaching: AbbVie, Merck, BMS, Gilead
Paul J. Pockros - Advisory Committees or Review Panels: Janssen, Merck, BMS,
Gilead, AbbVie; Consulting: Lumena, Beckman Coulter; Grant/Research Support:
Intercept, Janssen, BMS, Gilead, Lumena, Beckman Coulter, AbbVie, RMS,
Merck; Speaking and Teaching: AbbVie, Janssen, Gilead
Michael Robertson - Employment: Merck; Stock Shareholder: Merck
Peggy Hwang - Employment: Merck, Merck
Bach-Yen T. Nguyen - Employment: Merck
Janice Wahl - Employment: Merck & Co,
Eliav Barr - Employment: Merck
Rohit Talwani - Employment: Merck
Lawrence Serfaty - Advisory Committees or Review Panels: MSD, Janssen, Roche,
Gilead, BMS, Abbvie; Speaking and Teaching: Aptalis
The following authors have nothing to disclose: Jan Gerstoft