Albireo’s Lead Compound in Cholestatic Liver Diseases, A4250, Protects Against Bile Acid-Mediated Cholestatic Liver Injury in Mice

Albireo has announced that inhibition of ileal bile acid transport by A4250, the company’s lead compound for cholestatic liver diseases, protects against bile acid-mediated cholestatic liver injury in mice. The data was presented in an oral presentation titled “Inhibition of Intestinal Bile Acid Absorption by ASBT Inhibitor A4250 Protects Against Bile Acid-Mediated Cholestatic Liver Injury In Mice” at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL) in London, UK.

The study was performed in the laboratory of Professor Michael Trauner (Medical University, Vienna, Austria), a world leading expert in cholestatic liver diseases, using the mice Mdr2-/- model, a well established animal model of cholestatic liver injury. In the 4 week study, A4250 significantly decreased key cholestatic liver disease biomarkers, such as ALT, ALP and serum bile acids. In line with the biomarker findings, A4250 also reduced portal inflammation, as revealed by histological examination, and reduced pro-inflammatory biomarkers such as TNF-α, Mcp-1 and Vcam-1.

“The data in this trial clearly indicate that A4250 has beneficial effects on a broad range of biochemical liver function parameters and A4250 has potential as a novel hepatoprotective drug that may help preserve liver function in a number of chronic liver diseases such as PBC (primary biliary cirrhosis) and PSC (primary sclerosing cholangitis)” said Dr Hans Graffner, Chief Medical Officer at Albireo. A4250 decreases the re-absorption of bile acids and will reduce the toxic levels of bile acids in the liver cells of patients,  and studies in disease areas such as PBC, PSC and hereditary causes of cholestasis, such as progressive familial intrahepatic cholestasis (PFIC), are planned. Given the mode of action, A4250 should also be beneficial in liver diseases due to metabolic disturbances such as NASH (nonalcoholic steatohepatitis).