Mericitabine and ritonavir‐boosted danoprevir with or without ribavirin in treatment‐naive HCV genotype 1 patients: INFORM‐SVR study. (19th June 2014)

• Record Type: Journal Article
• Authors: Gane, Edward J.; Pockros, Paul J.; Zeuzem, Stefan; Marcellin, Patrick; Shikhman, Anna; Bernaards, Coen; Zhou, Julian; Yetzer, Ellen S.; Ballester, Rosa; Dwyer, Cindy; Tong, Xiao; Nájera, Isabel; Bertasso, Anne; Hammond, Janet; Kindrick, Amy; Morcos, Peter N.; Smith, Patrick; Stancic, Saray; Shulman, Nancy S.
• Is Part Of: Liver international. Volume 35(2015)Supplement 1
• Page Start: 79
• Page End: 89
• Publication Date: 2014-06-19
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12588
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12588-abs-0001"> <title>Abstract</title> <sec id="liv12588-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Safety and tolerability of peginterferon‐based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct‐acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir‐boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment‐naïve HCV genotype (G)1 infected patients.</p> </sec> <sec id="liv12588-sec-0002" sec-type="section"> <title>Methods</title> <p>Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks. Patients with HCV RNA <43 IU/ml between Weeks 2 and 8 and HCV RNA <15 IU/ml at Week 10 were rerandomized (1:1) at Week 12 to discontinue/continue assigned regimens until Week 24. Because of unacceptable relapse rates in both 12‐week arms and in ribavirin‐free Arm B, treatment was extended to 24 weeks and patients in Arm B received peginterferon alfa‐2a/ribavirin. The primary outcome was sustained virological response 24 weeks after end of treatment (SVR24).</p> </sec> <sec id="liv12588-sec-0003" sec-type="section"> <title>Results</title> <p>In Arm A, the SVR24 rate in patients receiving 24 weeks of therapy was 37.9% (25/66); 63.6% (14/22) in G1b and 25.0% (11/44) in G1a patients. Virologic breakthrough and relapse were associated with danoprevir‐resistant virus in most cases. The mericitabine‐resistance mutation (NS5BS282T) was detected in two patients bearing dual resistant virus NS3 R155K/NS5B S282T and dual resistance mutation L159F/L320F in one patient. Treatment was safe and well tolerated.</p> </sec> <sec id="liv12588-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Mericitabine, danoprevir/r plus ribavirin for 24 weeks were safe and well tolerated. However, SVR rates were poor, achieving rates of only 25.0% in G1a and 63.6% in G1b patients.</p> </sec> </abstract>