Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: The randomized PILLAR study

Authors


  • Potential conflict of interest: This study was funded by Janssen Research & Development, LLC. Editorial support was provided by Dr. Bethan Hahn, on behalf of Complete Medical Communications, funded by Janssen Research & Development, LLC. Dr. Fried has received research grants from, and serves as an ad hoc advisor to, Merck, Genentech, Vertex Pharmaceuticals, Tibotec/Janssen, Gilead, Bristol-Myers Squibb, Abbott, and AbbVie. Dr. Buti has participated in advisory boards and/or been a speaker for Merck, Sharpe and Dohme (MSD), Gilead, Vertex, Janssen, and Bristol-Myers Squibb. Dr. Dore has participated in an advisory committee for, and/or received financial support for research, teaching, or speaking, and/or received a travel scholarship from, Roche, Merck, Bristol-Myers Squibb, Janssen, AbbVie, and Gilead. Dr. Flisiak acts as an advisor for, and/or has received lecture fees from, Bristol-Myers Squibb, Gilead, Janssen, Merck, Novartis, Roche, and Vertex Pharmaceuticals. Dr. Ferenci was a member of an advisory board and speaker's bureau for Roche (Basel, Switzerland) and Rottapharm/Madaus (Monza, Italy), an advisor to Boehringer Ingelheim, Vertex Pharmaceuticals, Pfizer, Novartis, GlaxoSmithKline, Sanofi, and MSD, a consultant and advisor to Janssen, and receives an unrestricted research grant from Roche (Austria). Dr. Jacobson has received clinical research grants from, and/or was a consultant/advisor or member of a speaker's bureau for, Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Enanta, Gilead, GlaxoSmithKline, GlobeImmune, Inhibitex, Idenix, Kadmon, Novartis, Pfizer, Pharmasset, Presidio, Roche/Genentech, Schering/Merck, Tibotec/Janssen, Vertex Pharmaceuticals, and Zymogenetics. Dr. Marcellin has received grants and/or financial support for speaking or providing expert opinion for Roche, Schering-Plough, Gilead, Bristol-Myers Squibb, Vertex Pharmaceuticals, Novartis, Pharmasset, Tibotec, MSD, Boehringer Ingelheim, Biolex, Intermune, Alios BioPharma, Abbott, Pfizer, and Zymogenetics. Dr. Sherman consults and is on the speakers' bureau for Janssen, Vertex, and Merck. He also consults for Gilead and Boehringer Ingelheim. Dr. Zeuzem consults, advises, and is on the speakers' bureau for Janssen, Vertex, and Merck. Dr. Scott and Dr. De Smedt own stock in Janssen. Dr. Gilles, Dr. Peeters, and Dr. Sekar own stock in Johnson & Johnson.

  • This study was funded by Janssen Research & Development, LLC. Editorial support was provided by Dr. Bethan Hahn, on behalf of Complete Medical Communications, funded by Janssen Research & Development, LLC. M.W.F. is funded, in part, by NIH NIDDK Mid-Career Mentoring Award K24 DK066144.

Abstract

The phase IIb, double-blind, placebo-controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once-daily (QD) with pegylated interferon (Peg-IFN)-α-2a and ribavirin (RBV) in treatment-naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg-IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response-guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg-IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%-86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%-75.6% of SMV-treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%-86.1% of SMV-treated patients completed treatment by week 24; 85.2%-95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV. Conclusion: SMV QD in combination with Peg-IFN and RBV significantly improves SVR rates, compared with Peg-IFN and RBV alone, and allows the majority of patients to shorten their therapy duration to 24 weeks. (Hepatology 2013; 58:1918–1929)

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