TY - JOUR
T1 - A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1
AU - Lawitz, Eric
AU - Poordad, Fred
AU - Kowdley, Kris V.
AU - Cohen, Daniel E.
AU - Podsadecki, Thomas
AU - Siggelkow, Sara
AU - Larsen, Lois
AU - Menon, Rajeev
AU - Koev, Gennadiy
AU - Tripathi, Rakesh
AU - Pilot-Matias, Tami
AU - Bernstein, Barry
N1 - Funding Information:
Eric Lawitz: Research/Grant support: AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medarex, Medtronic, Merck & Co., Novartis, Pharmasset, Presidio, Roche, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Vertex Pharmaceuticals, ViroChem Pharma, ZymoGenetics, Speaker: Gilead, Kadmon, Merck, Vertex, Advisory Board Participation: AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, BioCryst, Biotica; Enanta; GlobeImmune, Idenix Pharmaceuticals, Inhibitex Pharmaceuticals, Janssen, Merck & Co., Novartis, Pharmasset, Santaris Pharmaceuticals, Tibotec, Theravance, Vertex Pharmaceuticals. Fred Poordad: Grant/Research support: Vertex, AbbVie, Boehringer Ingelheim, Merck, Anadys, GlaxoSmithKline, Novartis, Roche/Genentech, Idenix, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Janssen, Pharmaceuticals, Achillion Pharmaceuticals, BMS, Gilead, Pharmasset; Speaker: Vertex, Merck, Genentech; Consultant/Advisor: Vertex, AbbVie, Merck, Anadys Pharmaceuticals, Achillion, BMS, Gilead, Kadmon. Kris V. Kowdley: Grant/Research Support: AbbVie, Beckman Boehringer Ingelheim, BMS, Gilead/Pharmasset, Ikaria, Intercept, Janssen, Merck, Mochida, Vertex; Scientific Consulting: Novartis; Advisory Boards: AbbVie, Gilead, Merck, Vertex. Daniel E. Cohen, Thomas Podsadecki, Sara Siggelkow, Lois Larsen, Rajeev Menon, Gennadiy Koev, Rakesh Tripathi, Tami Pilot-Matias, and Barry Bernstein are AbbVie employees and may hold AbbVie or Abbott stock or options. The design, study conduct, analysis, and financial support of the clinical trials were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript.
PY - 2013/7
Y1 - 2013/7
N2 - Background & Aims: ABT-450 (combined with low-dose ritonavir, ABT-450/r) is a potent HCV NS3 protease inhibitor, and ABT-072 is a non-nucleoside NS5B polymerase inhibitor. The goal of this study was to evaluate the safety, tolerability, and efficacy of the peginterferon-free combination of ABT-450/r and ABT-072 with ribavirin in treatment-naïve patients with IL28B CC genotype, infected with HCV genotype 1. Methods: This was a phase 2a, multicenter, open-label, single-arm study in 11 treatment-naïve, non-cirrhotic HCV GT1-infected patients with IL28B rs12979860 genotype CC. Patients received ABT-450/r 150/100 mg once daily and ABT-072 400 mg once daily with weight-based ribavirin 1000-1200 mg/day dosed twice daily for 12 weeks. Results: Eight (73%) patients were male, 9 (82%) were Caucasian (including 3 who self-identified as Hispanic); mean baseline HCV RNA was 6.9 log10 IU/ml (range 6.5-7.3 log10 IU/ml). All 11 patients completed 12 weeks of treatment and maintained HCV RNA <25 IU/ml from weeks 4 through 12 of treatment. Ten patients (91%) achieved sustained virologic response 24 weeks post-treatment, with a second patient relapsing 36 weeks post-treatment. There were no deaths, serious or severe adverse events, or premature discontinuations. Adverse events were mostly mild and the most frequent were headache, fatigue, nausea, and dry skin. Conclusions: A 12-week regimen of ABT-450/r and ABT-072 with ribavirin was well tolerated with 9/11 patients achieving sustained virologic response through 36 weeks of post-treatment observation. These findings suggest that peginterferon-free regimens may have the potential to cure a high proportion of HCV genotype 1-infected patients.
AB - Background & Aims: ABT-450 (combined with low-dose ritonavir, ABT-450/r) is a potent HCV NS3 protease inhibitor, and ABT-072 is a non-nucleoside NS5B polymerase inhibitor. The goal of this study was to evaluate the safety, tolerability, and efficacy of the peginterferon-free combination of ABT-450/r and ABT-072 with ribavirin in treatment-naïve patients with IL28B CC genotype, infected with HCV genotype 1. Methods: This was a phase 2a, multicenter, open-label, single-arm study in 11 treatment-naïve, non-cirrhotic HCV GT1-infected patients with IL28B rs12979860 genotype CC. Patients received ABT-450/r 150/100 mg once daily and ABT-072 400 mg once daily with weight-based ribavirin 1000-1200 mg/day dosed twice daily for 12 weeks. Results: Eight (73%) patients were male, 9 (82%) were Caucasian (including 3 who self-identified as Hispanic); mean baseline HCV RNA was 6.9 log10 IU/ml (range 6.5-7.3 log10 IU/ml). All 11 patients completed 12 weeks of treatment and maintained HCV RNA <25 IU/ml from weeks 4 through 12 of treatment. Ten patients (91%) achieved sustained virologic response 24 weeks post-treatment, with a second patient relapsing 36 weeks post-treatment. There were no deaths, serious or severe adverse events, or premature discontinuations. Adverse events were mostly mild and the most frequent were headache, fatigue, nausea, and dry skin. Conclusions: A 12-week regimen of ABT-450/r and ABT-072 with ribavirin was well tolerated with 9/11 patients achieving sustained virologic response through 36 weeks of post-treatment observation. These findings suggest that peginterferon-free regimens may have the potential to cure a high proportion of HCV genotype 1-infected patients.
KW - Direct-acting antiviral
KW - Hepatitis C virus
KW - Interferon-free therapy
KW - Sustained virologic response
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U2 - 10.1016/j.jhep.2013.02.009
DO - 10.1016/j.jhep.2013.02.009
M3 - Article
C2 - 23439262
AN - SCOPUS:84879152382
SN - 0168-8278
VL - 59
SP - 18
EP - 23
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -