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At Intercept, our mission is to translate bile acid research into promising new treatments for liver diseases.

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At Intercept, our work is motivated by our desire to help patients and families who struggle with chronic liver diseases and need better treatment options.

Primary Biliary Cirrhosis

Overview of PBC

  • PBC is a liver disease that primarily results from autoimmune destruction of the bile ducts that transport bile acids (BAs) out of the liver, resulting in cholestasis
  • As PBC progresses, persistent toxic buildup of BAs causes progressive liver damage
  • If left untreated, or if a patient does not adequately respond to treatment, chronic inflammation and fibrosis can advance to cirrhosis
  • Disease progression in PBC is usually relatively slow, but can vary significantly
  • Data from published long-term studies demonstrate that a significant portion of patients with advancing disease progress to liver failure, transplant, or death within 5 to 10 years

Natural history of PBC

Natural history of PBC

  • In the silent preclinical phase, patients may be completely free of symptoms; however, in one study, despite otherwise normal serum biochemistry, patients with PBC tested positive for antimitochondrial antibodies (AMAs)
  • In the asymptomatic phase, patients may be diagnosed at an older age; length of survival can be shorter than for the general population
  • In the symptomatic phase, patients show more rapid progression to end-stage liver disease and have a worse prognosis than asymptomatic patients
  • In the preterminal phase, serum bilirubin increases and complications such as portal hypertension, ascites, and hepatic encephalopathy may develop as liver failure approaches
  • Falling rates of liver transplants for PBC since ursodeoxycholic acid (ursodiol) became widely used suggest a true change in natural history

Epidemiology of PBC

While PBC is rare, it is the most common cholestatic liver disease.

  • Incidence and prevalence vary geographically, ranging from 0.7 to 49 and 6.7 to 402 per million, respectively
  • In the United States, PBC is 1 of the top 10 most common causes of liver transplant
  • PBC is the second most common reason for liver transplant among women
  • PBC accounts for up to 2% of deaths from cirrhosis

Identifying patients with PBC

  • Approximate age of diagnosis is generally in the fifth decade of life
  • The presence of a concomitant autoimmune condition can signal increased risk for PBC, which should be evaluated and, if diagnosed, promptly treated with effective therapy
  • An estimated 90% of patients are women

Symptoms of PBC

A majority of patients with PBC are asymptomatic at the time of initial diagnosis, but most develop symptoms over time.

  • Initiation of symptoms such as fatigue accompanying PBC may not correlate with disease severity
  • Fatigue and pruritus are by far the most common symptoms accompanying PBC
  • Less common signs and symptoms include dry eyes and mouth as well as jaundice, which can be seen in more advanced disease

Potential complications of PBC

Outcomes may include, but are not limited to

  • Hypercholesterolemia
  • Hepatocellular carcinoma
  • Esophageal varices
  • Jaundice

Diagnosis of PBC

  • Based on American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines, clinical diagnosis of PBC is established based on 2 of 3 assessments:
    • A positive test for AMAs, seen in 95% of patients with PBC
    • Elevated serum levels of ALP
    • Liver biopsy, which may be used to confirm staging during the diagnosis of PBC

Treatment of PBC

  • Ursodiol is the standard of care for PBC
  • In studies in which ursodiol is administered early in the disease, at 13 to 15 mg/kg/day, it can improve serum biochemical markers and histological features
  • Ursodiol can delay progression of PBC
  • Patients who respond to therapy may demonstrate improved survival free of liver transplant
  • Approximately 40% of patients with PBC respond inadequately to long-term monotherapy with ursodiol
  • For patients who don’t adequately respond to ursodiol, treatment options are limited and novel approaches are needed

Development of OCA for PBC

  • Intercept is developing obeticholic acid (OCA) in the US and Europe for patients with PBC who have
    • Inadequate therapeutic response to ursodiol, the standard of care
    • Inability to tolerate ursodiol
  • OCA has fast track designation in the US and orphan drug designation in the US and Europe for the treatment of PBC

PBC resources for in-depth clinical information

  1. AASLD Practice Guidelines: Primary Biliary Cirrhosis (Lindor et al, Hepatology, July 2009)
  2. AASLD Endpoints Conference: Design and Endpoints for Clinical Trials in Primary Biliary Cirrhosis (Silveira et al, Hepatology, March 2010)
  3. Risk factors and prediction of long-term outcome in primary biliary cirrhosis (Ishibashi et al, Internal Medicine, Jan 2011)
  4. Farnesoid X receptor agonists for primary biliary cirrhosis. (Lindor, Current Opinions in Gastroenterology, May 2011)
  5. Primary biliary cirrhosis and bile acids (Corpechot, Clinics and Research in Hepatology and Gastroenterology, September 2012)
  6. The immunobiology and pathophysiology of primary biliary cirrhosis (Hirschfield et al, Annual Review of Pathology. January 2013)