Adult Liver Diseases

Albireo is studying new approaches for modulating acids with new compounds to address adult liver disease. Adult cholestatic diseases are a diverse group of disorders known for the appearance of jaundice, fatigue, pruritus and/or complications of cirrhosis. The most common adult cholestatic liver diseases are primary biliary cholangitis and primary sclerosing cholangitis.   

The Company has completed IND-enabling studies for a new preclinical candidate, A3907. A3907 is a selective apical sodium-dependent bile acid transporter (ASBT) inhibitor that has the potential to increase elimination of bile acids by both fecal and urinary excretion. In preclinical studies, A3907 showed a significant reduction in plasma levels of transaminases, total cholesterol and markers for cell damage, fibrosis, liver weight and liver total cholesterol levels.   

Sodium taurocholate co-transporting polypeptide (NTCP) inhibitors work by blocking bile entry into the liver and have shown promise in treating viral liver disease, like Hepatitis B and D, and other cholestatic liver diseases. Albireo is currently developing an oral NTCP inhibitor, including A2342, which is expected to begin IND-enabling studies this year.

About Nonalcoholic Steatohepatitis (NASH)

NASH is a common and serious chronic liver disease that resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. In NASH patients, fat accumulation in the liver, known as nonalcoholic fatty liver disease (NAFLD) or steatosis, and other factors such as high LDL cholesterol and insulin resistance induce chronic inflammation in the liver and may lead to progressive scarring of tissue, known as fibrosis, and cirrhosis, followed eventually by liver failure and death.

NASH is the fastest growing cause of liver transplantation in the United States and is a leading cause of hepatocellular carcinoma, the most common form of liver cancer. NASH patients have a ten-fold greater risk of liver-related mortality compared with the general population.

Based on an epidemiological study published in 2011, it is estimated that more than 10 percent of adults in the United States have NASH, representing over 30 million people. Although the prevalence of NASH is lower in children, it has also become a serious disease burden in the pediatric population. Other common co-existing conditions such as obesity and type 2 diabetes are important risk factors for NASH. From 1980 to 2010, the rate of obesity in the United States alone has more than doubled in adults and more than tripled in children 6 to 11 years of age and 12 to 19 years of age and has been projected to increase by an additional 33 percent over the next two decades. Globally, the rate of obesity has also nearly doubled since 1980 and is expected to double again by 2030 if not addressed.

NASH is typically a silent disease with few or no symptoms. Most people with NASH feel well and are not aware that they have a liver problem. Patients may only begin to have symptoms, such as fatigue, weight loss, and weakness, once the disease is more advanced or cirrhosis develops.