Medical Need and Market Opportunity
The patients with chronic liver disease that we intend to study suffer from compensated or decompensated liver cirrhosis (LC) as well as potentially portal hypertension (PH). The continual disease progression may eventually lead such patients to require liver transplantation, in which the diseased liver is replaced by a donor liver or part thereof. The cause of the chronic decompensation or liver failure may vary, and includes infections, such as subacute bacterial peritonitis, hepatitis C virus (HCV) or hepatitis B virus (HBV), metabolic causes, such as nonalcoholic steatohepatitis (NASH), autoimmune diseases and alcohol.
Eventually, these patients will progress to the point where, if eligible, they may require transplantation. Objectives for the management of patients with LC and PH include specific treatment of any identifiable causes of chronic liver function, such as HCV or HBV, and prevention of the development or progression of signs of decompensation, including portal pressure, ascites, hepatic encephalopathy and esophageal varices, with or without hemorrhage, in order for the patient to be eligible for transplant.
Independent published studies have shown that levels of caspase-cleaved Cytokeratin 18 (cCK18), a key biomarker of inflammation and apoptosis, are elevated in LC and PH patients and correlate with extent of liver inflammation and cholestasis. Approximately 32,000 patients die each year in the United States due to cirrhosis and its complications. Given its mechanism of action, emricasan has the potential to improve patients’ ability to survive longer with cirrhosis while waiting for a liver transplant and potentially to improve their liver disease status such that they may no longer require a liver transplant.