Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C†
Article first published online: 24 JUL 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 2, pages 324–329, August 2007
How to Cite
Pockros, P. J., Schiff, E. R., Shiffman, M. L., McHutchison, J. G., Gish, R. G., Afdhal, N. H., Makhviladze, M., Huyghe, M., Hecht, D., Oltersdorf, T. and Shapiro, D. A. (2007), Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C. Hepatology, 46: 324–329. doi: 10.1002/hep.21664
Potential conflict of interest: Dr. Shapiro is an employee and owns stock in Idun Pharmaceuticals. He is also a consultant for Pfizer, Inc. Dr. Oltersdorf is an employee and owns stock in Idun Pharmaceuticals. Dr. Pockros is a consultant for, advises, and received grants from Idun Pharmaceuticals. Dr. Schiff is a consultant for, received grants, and is on the speakers' bureau of Gilead, Ortho-Biotech, and Schering-Plough. He is also a consultant and received grants from Abbott, Bristol-Myers Squibb, Cadence Pharmaceuticals, GlaxoSmithKline, Idenix, Prometheus, Roche Molecular, and SciClone Pharmaceuticals. He is a consultant for Achillion Pharmaceutical, Cadence Pharmaceuticals, GlobeImmune, Inc., Pharmasset, Inc., Pfizer, Salix Pharmaceuticals, Inc., and Novartis/Idenix. Dr. Shiffman is a consultant and received grants from Idun Pharmaceuticals and Pfizer. Dr. McHutchison received grants from Idun Pharmaceuticals and Pfizer. Dr. Gish received grants, is a consultant, and is on the speakers' bureau of Bristol Myers Squibb, Eximias, F. Hoffmann-LaRoche Ltd., Gilead Sciences, InterMune Pharmaceuticals, Ortho Biotech, Schering-Plough Corp., SciClone Pharmaceuticals, Valeant Pharmaceuticals, PowderMed, and GlobeImmnue. He also received grants from Pfizer, Idun Pharmaceuticals, and Idenix/Novartis. He is also a consultant and is on the speakers' bureau for Bayer AG and GlaxoSmithKline. He is a consultant for Amgen Inc., Anadys Pharmaceuticals, Inc., Chiron Corp., Corixa Corp., Human Genome Sciences, Metabasis Therapeutics, United Therapeutics, XTL Biopharmaceuticals, Zymogenetics, Inc., Pharmaseet, Idenix, Hepahope, Nucleonics, and Innogenetics. He is on the speakers' bureau of Salix. Dr. Afdhal advises and received grants from Idun Pharmaceuticals.
- Issue published online: 27 JUL 2007
- Article first published online: 24 JUL 2007
- Manuscript Accepted: 22 JAN 2007
- Manuscript Received: 20 NOV 2006
- Idun Pharmaceuticals, Inc., now owned by Pfizer, Inc.
Increased rates of apoptosis (programmed cell death) have been demonstrated in many hepatic diseases including chronic hepatitis C. IDN-6556 is a potent inhibitor of caspases, the proteases that execute apoptosis. In a prior phase 1 study, IDN-6556 lowered aminotransferase activity in a small number of patients with liver impairment. The purpose of this study was to further explore the effect of IDN-6556 in patients with liver disease in a multicenter, double-blind, placebo-controlled, dose-ranging study with a 14-day dosing period. A total of 105 patients were enrolled in the study; 79 received active drug; 80 patients had chronic hepatitis C and 25 had other liver diseases including nonalcoholic steatohepatitis (NASH), hepatitis B, primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). IDN-6556 doses ranged from 5 mg to 400 mg daily, given from 1 to 3 times per day. In the HCV patients, all doses of IDN-6556 significantly lowered ALT and AST (P = 0.0041 to P < 0.0001 for various dosing groups in Wilcoxon tests comparing IDN-6556 to placebo), with the exception of the lowest dose. Declines in aminotransferase activity were also seen in patients with NASH but effects were not apparent in the small number of other liver diseases. Adverse experiences were not different between IDN-6556 and placebo. There were no clinically meaningful changes in other laboratory parameters. In particular, mean HCV RNA levels did not show significant changes. Conclusion: Oral IDN-6556, given for 14 days, significantly lowered aminotransferase activity in HCV patients and appeared to be well tolerated. Longer studies to assess potential effects of IDN-6556 on liver inflammation and fibrosis are merited. (HEPATOLOGY 2007.)