Article first published online: 12 JUN 2013
Copyright © 2013 American Association for the Study of Liver Diseases
Volume 57, Issue 6, pages 2155–2163, June 2013
How to Cite
Sulkowski, M. S., Bourlière, M., Bronowicki, J.-P., Asselah, T., Pawlotsky, J.-M., Shafran, S. D., Pol, S., Mauss, S., Larrey, D., Datsenko, Y., Stern, J. O., Kukolj, G., Scherer, J., Nehmiz, G., Steinmann, G. G. and Böcher, W. O. (2013), Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial. Hepatology, 57: 2155–2163. doi: 10.1002/hep.26386
Potential conflict of interest: Dr. Sulkowski advises and received grants from Abbott, Boehringer Ingleheim, Bristol-Myers Squibb, Janssen, Merck, Roche, and Vertex. He advises Gilead, Novartis, and Pfizer. Dr. Bronowicki consults for Boehringer Ingleheim. Dr. Asselah consults for, advises, received grants from, and is on the speakers' bureau for Boehringer Ingleheim. Dr. Pawlotsky advises and received grants from Gilead and Roche. He also advises Abbott, Achillion, Anadys, Biotica, Boehringer Ingleheim, Bristol-Myers Squibb, Janssen-Cilag, Madaus-Rottapharm, Merck, and Novartis. Dr. Shafran advises and received grants from Merck, Pfizer, Roche, Abbott, Bristol-Myers Squibb, Gilead, and Vertex. He received grants from Boehringer Ingleheim and GSK. He advises Janssen. Dr. Pol received grants from and is on the speakers' bureau for Bristol-Myers Squibb, Boehringer Ingleheim, Gilead, Novartis, MSD, and Janssen. Dr. Mauss advises and is on the speakers' bureau for Boehringer Ingleheim and Roche. Dr. Larrey consults, received grants from, and is on the speakers' bureau for Roche. He consults for and received grants from Boehringer Ingleheim, Bristol-Myers Squibb, and Gilead. He consults and is on the speakers' bureau for Merck. He received grants from Abbott.
Supported by Boehringer Ingelheim Pharma GmbH & Co KG.
- Issue published online: 12 JUN 2013
- Article first published online: 12 JUN 2013
- Accepted manuscript online: 15 MAR 2013 07:47AM EST
- Manuscript Accepted: 23 FEB 2013
- Manuscript Revised: 19 FEB 2013
- Manuscript Received: 25 JAN 2013
Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor. In all, 290 noncirrhotic HCV genotype (GT)-1 patients with prior null (<1 log10 viral load [VL] drop at any time on treatment) or partial response (≥1 log10 VL drop but never undetectable on treatment) were randomized 2:1:1 to receive 48 weeks of peginterferon alfa-2a and ribavirin (PegIFN/RBV) in combination with faldaprevir 240 mg once daily (QD) with 3 days PegIFN/RBV lead-in (LI), 240 mg QD without LI, or 240 mg twice daily (BID) with LI. Patients in the 240 mg QD/LI group achieving maintained rapid virologic response (mRVR; VL <25 IU/mL [Roche TaqMan] at week 4 and undetectable at weeks 8 to 20) were rerandomized to cease all treatment at week 24 or continue PegIFN/RBV up to week 48. Sustained virologic response (SVR) rates were 32%, 50%, and 42% in prior partial responders, and 21%, 35%, and 29% in prior null responders in the faldaprevir 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. In the 240 mg QD/LI group, a significantly higher proportion of mRVR patients rerandomized to 48 weeks' treatment achieved SVR compared with those assigned to 24 weeks treatment (72% versus 43%; P = 0.035). Rates of gastrointestinal disorders, jaundice, dry skin, and photosensitivity were increased at 240 mg BID compared with the 240 mg QD dose. Faldaprevir discontinuations owing to adverse events occurred in 6%, 4%, and 23% of patients in the 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. Conclusion: Faldaprevir 240 mg QD with PegIFN/RBV was safe and tolerable and produced substantial SVR rates in prior null and partial responders. The 240 mg QD dose is currently undergoing phase 3 evaluation. (Hepatology 2013;57:2155–2163)