A4250 is a potent and selective inhibitor of the ileal bile acid transporter (IBAT), sometimes also referred to as the apical sodium dependent bile acid transporter (ASBT), that has minimal systemic exposure at therapeutic doses and acts locally in the gut. In an open label Phase 2 study in children with cholestatic liver disease and pruritus, A4250 showed reductions in serum bile acids and pruritus in most patients and exhibited a favorable overall tolerability profile.
We are developing A4250 initially to treat patients with PFIC, a rare genetic liver disease, and plan to consider additional development in other pediatric cholestatic liver diseases and disorders in the future. Our Phase 3 program in PFIC includes a single randomized, double-blind, placebo-controlled, multicenter clinical trial and an open-label long-term extension study. The double-blind trial, called PEDFIC-1, is now underway and is designed to enroll approximately 60 patients with PFIC (subtypes 1 or 2), ages 6 months to 18 years, at sites in the United States, Canada, Europe, the Middle East and Australia.
A4250 has been granted orphan drug designation for PFIC in the United States and the European Union, granted rare pediatric disease designation by the FDA and granted access to the PRIority MEdicines (PRIME) program of the European Medicines Agency (EMA) for the treatment of PFIC.
When the flow of bile from the liver stops or is disrupted, known as cholestasis, bile acids accumulate in the liver. Elevated bile acid levels in the liver and serum are primary characteristics of cholestatic liver diseases and have been linked to severe pruritus in these patients. The IBAT is primarily responsible for mediating the uptake of bile acids from the small intestine to the liver as part of a process known as enterohepatic circulation. Typically, approximately 95 percent of bile acids are recirculated via the IBAT to the liver. Accordingly, a product capable of inhibiting the IBAT could lead to a reduction in bile acids returning to the liver and may represent a promising approach for treating cholestatic liver diseases.
Products described on this Website, with the exception of elobixibat for chronic constipation in Japan, are investigational new drugs, and are not approved for use or commercially available.