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.
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.
Authors: David E Kleiner; Paul D Berk; Jesse Y Hsu; Anita P Courcoulas; David Flum; Saurabh Khandelwal; John Pender; Alfons Pomp; James Roerig; Laura L Machado; Bruce M Wolfe; Steven H Belle Journal: Semin Liver Dis Date: 2014-04-29 Impact factor: 6.115
Authors: Anita Kohli; Anuoluwapo Osinusi; Zayani Sims; Amy Nelson; Eric G Meissner; Lisa L Barrett; Dimitra Bon; Miriam M Marti; Rachel Silk; Colleen Kotb; Chloe Gross; Tim A Jolley; Sreetha Sidharthan; Tess Petersen; Kerry Townsend; D'Andrea Egerson; Rama Kapoor; Emily Spurlin; Michael Sneller; Michael Proschan; Eva Herrmann; Richard Kwan; Gebeyehu Teferi; Rohit Talwani; Gabbie Diaz; David E Kleiner; Brad J Wood; Jose Chavez; Stephen Abbott; William T Symonds; G Mani Subramanian; Phillip S Pang; John McHutchison; Michael A Polis; Anthony S Fauci; Henry Masur; Shyam Kottilil Journal: Lancet Date: 2015-01-13 Impact factor: 79.321
Authors: Ryan C Schoenfeld; David L Bourdet; Ken A Brameld; Elbert Chin; Javier de Vicente; Amy Fung; Seth F Harris; Eun K Lee; Sophie Le Pogam; Vincent Leveque; Jim Li; Alfred S-T Lui; Isabel Najera; Sonal Rajyaguru; Michael Sangi; Sandra Steiner; Francisco X Talamas; Joshua P Taygerly; Junping Zhao Journal: J Med Chem Date: 2013-10-10 Impact factor: 7.446