Primary sclerosing cholangitis (PSC) is a rare, serious, idiopathic chronic cholestatic liver disease characterized by progressive inflammation and destruction of bile ducts, which may lead to fibrosis, cirrhosis, portal hypertension, cancer, and ultimately liver failure. It is estimated that approximately 29,000 people in the United States and approximately 50,000 people in Europe suffer from PSC.
PSC pathogenesis is complex, involves hereditary and environmental factors, and remains poorly understood. There is evidence that variations in certain genes involved with bile acid synthesis/transport as well as elevated levels of bile acids are associated with the development of PSC as well disease severity and progression. The median age at diagnosis is approximately 35 years and approximately 70% of PSC patients have inflammatory bowel disease, principally ulcerative colitis.
The earliest symptoms of PSC include extreme fatigue, abdominal discomfort, and pruritus. Up to 70% of PSC patients suffer from pruritus during the course of the disease. As the condition worsens, patients may develop jaundice and enlarged spleens. Eventually, the buildup of bile damages liver cells and contributes to the progression of the disease from chronic liver disease to subsequent liver failure. Median transplant-free survival for PSC patients is estimated to be nine to 18 years from diagnosis in symptomatic patients, depending upon the stage of the disease at the time of diagnosis. Complications involving the biliary tree are common and include cholangitis, as well as ductal strictures, and gallstones, both of which may require frequent endoscopic or surgical interventions. PSC increases the risk of development of malignancies, with cholangiocarcinoma, a group of cancers that begin in the bile ducts, being the most common.
There is a need for novel therapeutic interventions in PSC as liver transplantation is currently the only known treatment shown to improve clinical outcomes. UDCA is often used off-label for the treatment of PSC but does not offer improvement in pruritus, one of the most debilitating symptoms associated with the disease. PSC is the fifth leading indication for liver transplantation; however, the post-transplant recurrence rate of PSC is as high as 25%. We believe an ASBTi offers a substantial opportunity to address many of the symptoms and associated complications of PSC, as well as potentially delay or eliminate the need for liver transplantation.