Swedish biotechnology firm Albireo has started a Phase II trial of its lead compound A4250, for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH).
The company said that A4250 acts locally in the gut to inhibit the ileal sodium dependent bile acid transporter (IBAT).
The Phase II cross-over trial, being conducted at the Sahlgrenska Academy, Göteborg, Sweden, is led by Professor Hanns-Ulrich Marschall, an expert in the field of liver diseases and bile acid modulation.
The trial is designed evaluate the efficacy and safety of once daily A4250 in patients with primary biliary cirrhosis (PBC) and cholestatic pruritus.
Apart from the evaluation of changes in pruritus (itching), the trial will focus on changes in liver parameters known to be predictors of disease progression in liver diseases in general.
Marschall said: "There is a real need for novel therapies in this area and A4250 clearly has the potential as a novel hepatoprotective drug that may help improve liver function in patients with a variety of chronic liver diseases.
"In Phase I studies, A4250 has shown to be safe and shown clear effects on a number of key pharmacodynamic markers, including significant, dose-dependent lowering of serum bile acids. Serum bile acids are commonly increased in cholestatic liver diseases."
The company said that 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.
Albireo chief medical officer Dr Hans Graffner said: "The safety and efficacy of A4250 in both preclinical and Phase I studies are encouraging and strongly support development of A4250 in cholestatic liver diseases.
"Given the mode of action, A4250 should also be beneficial in liver diseases due to metabolic disturbances such as NASH (nonalcoholic steatohepatitis).
"In addition to the effects on bile acids, the beneficial effects on LDL cholesterol and GLP-1 should be of importance in the treatment of NASH."
The company’s double-blind single and multiple ascending dose Phase I trial evaluated the safety, pharmacokinetics and pharmacodynamics of A4250 in healthy subjects and there were no serious adverse events reported.
Image: High magnification micrograph of steatohepatitis. Photo: courtesy of Nephron