Date: 2014-04-11
Type of information:
phase:
Announcement:
Company: Albireo (Sweden)
Product: A4250
Action
mechanism: A4250 is a highly potent inhibitor of the apical sodium dependent bile acid transporter (ASBT). A4250 decreases the re-absorption of bile acids and will thereby reduce the toxic levels of bile acids in the liver cells of patients with cholestatic liver disease. Importantly, A4250 also will reduce the increased levels of serum bile acids seen in these patients. A4250 acts locally in the gut with only minimal systemic exposure; thereby the risk for potential systemic side effects will be reduced. A4250 is currently in phase I clinical studies and plans are to move the program into cholestatic liver disease patients later this year. A4250 has received orphan drug designation for PBC and PFIC both from the FDA and the European Medicines Agency.
Disease:
Therapeutic area: Metabolic diseases - Liver diseases
Country:
Trial details:
Latest
news: * On April 11, 2014, 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 have been 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.
