studies

228A AASLD ABSTRACTS HEPATOLOGY, October, 2015
patients ± cirrhosis ± HIV co-infection. Injection drug use is the
major risk factor for HCV transmission in many settings; however,
data on interferon-free treatment outcomes among PWID
are very limited. C-EDGE COSTAR is a Phase 3 trial evaluating
efficacy and safety of GZR/EBR among treatment naïve
HCV GT1/4/6-infected patients ± cirrhosis who are receiving
opioid agonist therapy (OAT) (methadone or buprenorphine).
METHODS: This double-blind, placebo-controlled study randomized
patients 2:1 to an immediate treatment group (ITG) or
a deferred treatment group (DTG). The ITG received GZR/
EBR for 12 weeks; the DTG received placebo for 12 weeks,
followed by 12 weeks of open label GZR/EBR. Use of non-prescribed
drugs was monitored by urine drug screening, but
was not exclusionary to study participation. HCV RNA levels
were measured using COBAS TaqMan v2.0 (lower limit of
quantitation 5x
ULN after normalization while on therapy. SVR12 results will
be presented. CONCLUSION: Preliminary data indicate that
GZR/EBR is safe and highly effective in patients with chronic
HCV GT1, 4, or 6 receiving OAT, and supports enhanced
efforts to address barriers to HCV treatment access for PWID.
Disclosures:
Gregory Dore - Board Membership: Gilead, Merck, Abbvie, Bristol-Myers
Squibb; Grant/Research Support: Gilead, Merck, Abbvie, Bristol-Myers Squibb;
Speaking and Teaching: Gilead, Merck, Abbvie, Bristol-Myers Squibb
Frederick Altice - Grant/Research Support: Gileaad, NIH, NIDA, SAMHSA,
HRSA; Speaking and Teaching: Merck, Bristol Myers Squibb, Gilead, Rush Practice
Point Communications
Alain H. Litwin - Advisory Committees or Review Panels: Merck, Gilead; Grant/
Research Support: Merck, Gilead
Olav Dalgard - Advisory Committees or Review Panels: MSD, Janssen Cilag,
Medivir, Gilead, Abbvie; Grant/Research Support: MSD, Medivir, Gilead
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
Anne Luetkemeyer - Grant/Research Support: Gilead, Abbvie, Pfizer, Bristol
Myers Squibb, Merck
Ronald Nahass - Advisory Committees or Review Panels: Gilead, MErck, Janssen,
BMS; Grant/Research Support: Gilead, Merck, Janssen, BMS; Speaking and
Teaching: Gilead, Merck, Janssen
Cheng-Yuan Peng - Advisory Committees or Review Panels: AbbVie, BMS, Gilead,
MSD, Roche
Brian Conway - Advisory Committees or Review Panels: Vertex Pharmaceuticals,
Merck, Boehringer Ingelheim, Jannsen Pharmaceuticals; Grant/Research Support:
Vertex Pharmaceuticals, Merck, Boehringer Ingelheim, Jannsen Pharmaceuticals,
AbbVie, Gilead Sciences, Gilead Sciences
Jason Grebely - Advisory Committees or Review Panels: Merck, Gilead; Grant/
Research Support: Merck, Gilead, Abbvie, BMS
Anita Y. Howe - Employment: Merck Research Laboratory
Bach-Yen T. Nguyen - Employment: Merck
Janice Wahl - Employment: Merck & Co,
Eliav Barr - Employment: Merck
Michael Robertson - Employment: Merck; Stock Shareholder: Merck
The following authors have nothing to disclose: Oren Shibolet, Heather L. Platt
41
98%–100% SVR4 in HCV Genotype 1 Non-Cirrhotic
Treatment-Naïve or Pegylated Interferon/Ribavirin Null
Responders With the Combination of the Next Generation
NS3/4A Protease Inhibitor ABT-493 and NS5A
Inhibitor ABT-530 (SURVEYOR-1)
Fred Poordad 2 , Franco Felizarta 3 , Armen Asatryan 1 , Tarek I. Hassanein
4 , Humberto I. Aguilar 5 , Jacob P. Lalezari 6 , J. Scott Overcash
7 , Teresa Ng 1 , Ran Liu 1 , Chih-Wei Lin 1 , Federico J. Mensa 1 ,
Jens Kort 1 ; 1 AbbVie, Inc., North Chicago, IL; 2 Texas Liver Institute,
University of Texas Health Science Center, San Antonio, TX; 3 Private
practice, Bakersfield, CA; 4 Southern California GI and Liver
Centers and Southern California Education and Research Center,
Coronado, CA; 5 Louisiana Research Center, Shreveport, LA;
6 Quest Clinical Research, San Francisco, CA; 7 eStudySite, San
Diego, CA
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 pangenotypic in vitro antiviral activity
against major HCV genotypes (GTs), including activity against
key known resistance-associated variants and a high barrier
to resistance selection. Monotherapy with ABT-493 or ABT-
530 resulted in a mean 4 log 10
IU/mL decline from baseline
in HCV plasma viral load in GT1-infected subjects with and
without compensated cirrhosis. Purpose: In this phase 2 study,
treatment with ABT-493 and ABT-530 for 12 weeks is evaluated
in HCV GT1-infected subjects without cirrhosis. Efficacy
and safety results are reported here. Methods: Non-cirrhotic
GT1-infected treatment-naïve (TN) or pegylated interferon/ribavirin
(pegIFN/RBV) null responder subjects received once-daily
ABT-493 200 mg + ABT-530 120 or 40 mg for 12 weeks,
and subsequently were followed for 24 weeks. The primary
efficacy endpoint was sustained virologic response 12 wks
after the last dose of study drug (SVR12). Safety was evaluated
by adverse event (AE) monitoring, laboratory testing,
and other standard assessments. Results: 79 subjects (male,
52%; median [range] age, 54.0 [26.0–70.0] years; GT1a,
81%; GT1b, 19%; TN, 63%; pegIFN/RBV null responders,
37%; fibrosis >F2, 25%; median [range] HCV RNA log 10
IU/
mL, 6.8 [4.4–7.5]) were enrolled, 40 received ABT-493 200
mg+ABT-530 120 mg and 39 received ABT-493 200 mg and
ABT-530 40 mg. SVR 4 weeks after the last dose of study drug
(SVR4) is available in all 79 subjects. SVR4 was achieved in
29 of 29 (100%) pegIFN/RBV null responders and 49 of 50
(98%) TN subjects. One TN subject relapsed at post-treatment
week 4; further characterization of this relapse and complete
post-treatment week 12 data (SVR12) will be available. There
were no treatment-related serious AEs or clinically relevant
laboratory findings. The most common AEs (reported in >5%
of subjects) were fatigue, headache, nausea, diarrhea, and
anxiety. Conclusions: Once-daily 12-week treatment with the
next-generation HCV DAAs ABT-493 and ABT-530 of GT1
infection in non-cirrhotic TN and pegIFN/RBV null responders
resulted in high SVR4 (98%–100%) rates. One treatment
relapse was observed. Based on these encouraging results,
the SURVEYOR-1 study with once-daily ABT-493 and ABT-530
has been expanded to include GT1 subjects with compensated
cirrhosis and evaluate a shorter, 8 week treatment duration in
non-cirrhotic subjects.