Albireo’s Lead Compound In Cholestatic Liver Diseases, A4250, Protects Against Bile Acid-Mediated Cholestatic Liver Injury In Mice
4/11/2014 9:49:51 AM
Gothenburg, Sweden, April 11, 2014 / B3C newswire / - Albireo today 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 will be presented tomorrow 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-a, 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).
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 U.S. Food & Drug Administration and the European Medicines Agency.
Albireo is a Swedish biotechnology company focused on the development of novel therapeutics for the treatment of gastrointestinal and liver diseases. The company has extensive experience in the development of ASBT modulators and currently has two ASBT inhibitors in clinical development, elobixibat and A4250. Elobixibat is in Phase III in chronic constipation and is also in development for IBS with constipation. Elobixibat is partnered with Ferring and with Ajinomoto. In addition to ASBT inhibitors, Albireo has a pipeline of drug candidates for the development in areas such as IBD. The Albireo management team has a broad experience in drug development and has an extensive network in the international scientific and clinical communities. Albireo was created as a spin-out of AstraZeneca in 2008, financed by a syndicate of leading healthcare investors, led by Phase4 Ventures, and joined by TPG Biotech, TVM Capital and Scottish Widows Partnership.
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