Emricasan Clinical Data
Publications
Clinical trial: The efficacy and safety of oral PF-03491390, a pancaspase inhibitor – a randomized placebo-controlled study in patients with chronic hepatitis C
Shiffman ML et al. Aliment Pharmacol Ther. 2010 May; 31(9):969-78.
DOI: 10.1111/j.1365-2036.2010.04264.x
Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C
Pockros PJ et al. Hepatology. 2007 Aug; 46(2):324-9.
DOI: 10.1002/hep.21664
Posters & Abstracts
Physiologically normal levels of apoptosis in healthy volunteers are not reduced by the pan-caspase inhibitor, emricasan
Spada AP et al. Poster presented at AASLD November 2013.
Abstract 1532 (949A): Hepatology, 58: 943A-950A.
DOI: 10.1002/hep.26869
Inhibition of caspase activity with emricasan in HCV patients: Potential implications for chronic dosing and long term safety
Spada AP et al. Poster presented at AASLD November 2012.
Abstract 2006 (1123A): Hepatology, 56: 191A-1144A.
DOI: 10.1002/hep.26040
PF-03491390 inhibits liver fibrosis in patients with chronic hepatitis C virus infection via suppression of pro-apoptotic caspase-activation
Burgess G et al. Abstract for AASLD October 2007.
Abstract 1307 (818A): Hepatology, 46: 725A-821A.
DOI: 10.1002/hep.22021
Emricasan Preclinical Data
Publications
Caspase inhibitor IDN6556 facilitates marginal mass islet engraftment in a porcine islet autotransplant model
McCall MD et al. Transplantation. 2012 Jul 15;94(1):30-5.
DOI: 10.1097/TP.0b013e318257745d.
The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice
McCall M et al. Surgery. 2011 Jul;150(1):48-55.
DOI: 10.1016/j.surg.2011.02.023.
Orally-administered caspase inhibitor PF-03491390 is retained in the liver for prolonged periods with low systemic exposure, exerting a hepatoprotective effect against a-Fas-induced liver injury in a mouse model
Ueno Y et al. J Pharmacol Sci. 2007 Oct;105(2):201-5.
DOI: 10.1254/jphs.SC0070207
A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia
Hoglen NC et al. Liver Transpl. 2007 Mar;13(3):361-6.
DOI: 10.1002/lt.21016
Caspase inhibition improves ischemia-reperfusion injury after lung transplantation
Quadri SM et al. Am J Transplant. 2005 Feb;5(2):292-9.
DOI: 10.1111/j.1600-6143.2004.00701.x
Characterization of IDN-6556 (3-{2-(2-tert-Butylphenylaminooxalyl)-amino]-propionylamino}-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid): a Liver-Targeted Caspase Inhibitor
Hoglen NC et al. J Pharmacol Exp Ther. 2004 May;309(2):634-40.
DOI: 10.1124/jpet.103.062034
The caspase inhibitor IDN-6556 attenuates hepatic injury and fibrosis in the bile duct ligated mouse
Canbay A et al. J Pharmacol Exp Ther. 2004 Mar;308(3):1191-6.
DOI: 10.1124/jpet.103.060129
Posters & Abstracts
Safety and efficacy of the pan-caspase inhibitor IDN-6556 on the treatment of non-alcoholic fatty liver and insulin resistance
Lu W et al. Poster Presented at EASL April 2013.
Abstract 1296 (S523): J Hepatol 2013 Apr;58:S409-S566
DOI: 10.1016/S0168-8278(13)61297-0
Pan-Caspase Inhibition Protects Against Fibrotic NASH Induced By Choline Deficient Amino Acid Defined Diet (CDAA)
Lu W et al. Poster Presented at EASL April 2013.
Abstract 292 (S123): J Hepatol 2013 Apr;58:S63-S227
DOI: 10.1016/S0168-8278(13)61295-7
PF-03491390 pan-caspase inhibitor decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis (NASH)
Barreyro FJ et al. Poster presented at EASL April 2010.
Abstract 779 (S303): J Hepatol 2010 Apr;52:S183-S317.
DOI: 10.1016/S0168-8278(10)60781-7
Mechanism of Action Resources
Apoptosis
Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection
Patin E et al. Gastroenterology. 2012 Nov;143(5):1244-52.e1-12.
DOI: 10.1053/j.gastro.2012.07.097
Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
Galluzzi L et al. Cell Death Differ. 2012 Jan;19(1):107-20.
DOI: 10.1038/cdd.2011.96
Apoptosis and acute kidney injury
Havasi A and Borkan SC. Kidney Int. 2011 Jul;80(1):29-40.
DOI: 10.1038/ki.2011.120
Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression
Canbay A et al. Hepatology. 2003 Nov;38(5):1188-98.
DOI: 10.1053/jhep.2003.50472
Biomarkers
Reduction in hepatic inflammation is associated with less fibrosis progression and fewer clinical outcomes in advanced hepatitis C
Morishima C et al. Am J Gastroenterol. 2012 Jun 12.
DOI: 10.1038/ajg.2012.137
Elevated serum CK18 levels in chronic hepatitis C patients are associated with advanced fibrosis but not steatosis
Jazwinski AB et al. J Viral Hepat. 2012 Apr;19(4):278-82.
DOI: 10.1111/j.1365-2893.2011.01546.x
Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease
Kim WR et al. Hepatology. 2008 Apr;47(4):1363-70.
DOI: 10.1002/hep.22109
Serum aminotransferase activity and mortality risk in a United States community
Lee TH et al. Hepatology. 2008 Mar;47(3):880-7.
DOI: 10.1002/hep.22090
Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C
Kronenberger WB et al. J Viral Hepat. 2005 May;12(3):307-14.
DOI: 10.1111/j.1365-2893.2005.00594.x
Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study
Kim HC et al. BMJ. 2004 Apr 24;328(7446):983
DOI: 10.1136/bmj.38050.593634.63
Liver Disease Resources
ACLF
Toward an improved definition of acute-on-chronic liver failure
Jalan R et al. Gastroenterology. 2014 Jul;147(1):4-10.
DOI: 10.1053/j.gastro.2014.05.005
Acute-on-chronic liver failure: A review
Zamora Nava LE et al. Ther Clin Risk Manag. 2014 Apr 23;10:295-303. DOI: 10.2147/TCRM.S59723
Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis
Moreau R et al. Gastroenterology. 2013 Jun;144(7):1426-37, 1437.e1-9. DOI: 10.1053/j.gastro.2013.02.042
Monitoring oxidative stress in acute-on-chronic liver failure by advanced oxidation protein products
Liu H et al. Hepatol Res. 2012 Feb;42(2):171-80.
DOI: 10.1111/j.1872-034X.2011.00911.x
Liver histology as predictor of outcome in patients with acute-on-chronic liver failure (ACLF)
Rastogi A et al. Virchows Arch. 2011 Aug;459(2):121-7.
DOI: 10.1007/s00428-011-1115-9
CLF
Elevated apoptosis-associated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation
Yagmur E et al. Clin Biochem. 2007 Jun;40(9-10):651-5.
DOI: 10.1016/j.clinbiochem.2006.12.010
POLT-HCV
Reversal, maintenance or progression: What happens to the liver after a virologic cure of hepatitis C?
Lee YA and Friedman SA. Antiviral Res. 2014 Jul;107C:23-30.
DOI: 10.1016/j.antiviral.2014.03.012
My Treatment Approach to Chronic Hepatitis C Virus
Shiffman ML et al. Mayo Clin Proc. 2014 May 24.
DOI: 10.1016/j.mayocp.2014.04.013
Progression of liver fibrosis in post-transplant hepatitis C: Mechanisms, assessment and treatment
Berenguer M and Schuppan D. J Hepatol. 2013 May;58(5):1028-41.
DOI: 10.1016/j.jhep.2012.12.014
Accelerated liver disease in aggressive hepatitis C recurrence post-liver transplantation may be due to enhanced apoptosis mediated by both virus and immunosuppressants
Lim EJ et al. Poster Presented at EASL April 2013.
Abstract 1179 (S479): J Hepatol 2013 Apr;58:S409-S566
DOI: 10.1016/S0168-8278(13)61180-0
Ishak stage and quantitative fibrosis measurement (collagen proportionate area) progression in post liver transplant (post-LT) patients with chronic hepatitis C infection
Ma G et al. Poster presented at AASLD November 2012.
Abstract 1228 (777A): Hepatology, 56:191A-1144A.
DOI: 10.1002/hep.26040
A semi-mechanistic model of fibrosis progression using collagen proporationate are (CPA) in post liver transplant (POLT) patients with chronic hepatitis C (CHC)
Ma G et al. Poster presented at World Conference on Pharmacometrics September 2012.
Ishak stage progression model in post liver transplant (POLT) patients with chronic hepatitis C virus (HCV) infection
Ma G et al. Poster presented at World Conference on Pharmacometrics September 2012.
Enhanced apoptosis in post-liver transplant hepatitis C: Effects of virus and immunosuppressants
Lim EJ et al. World J Gastroenterol. 2012 May 14;18(18):2172-9.
DOI: 10.3748/wjg.v18.i18.2172
Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5 year follow-up of 150 patients
George SL et al. Hepatology. 2009 Mar;49(3):729-38.
DOI: 10.1002/hep.22694
Reversibility of Liver Fibrosis and Cirrhosis Following Treatment for Hepatitis C
Arthur MJ. Gastroenterology. 2002 May;122(5):1525-8.
DOI: 10.1053/gast.2002.33367
NAFLD/NASH
Radiologic evaluation of nonalcoholic fatty liver disease
Lee SS and Park SH. World J Gastroenterol. 2014 Jun 21;20(23):7392-7402.
Controversies in the Diagnosis and Management of NAFLD and NASH
Rinella ME et al. Gastroenterol Hepatol (N Y). 2014 Apr;10(4):219-27.
Review article: Is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions?
Yilmaz Y. Aliment Pharmacol Ther. 2012 Nov;36(9):815-23
DOI: 10.1111/apt.12046
A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients
Anty R et al. Aliment Pharmacol Ther. 2010 Dec;32(11-12):1315-22.
DOI: 10.1111/j.1365-2036.2010.04480.x
Apoptosis and cytokines in non-alcoholic steatohepatitis
Syn WK et al. Clin Liver Dis. 2009 Nov;13(4):565-80.
DOI: 10.1016/j.cld.2009.07.003