Albireo presents data from Phase 2 clinical trial evaluating A4250
Albireo Pharma announced that results in Alagille syndrome and biliary atresia patients from its completed Phase 2 clinical trial evaluating A4250 in pediatric cholestasis were presented at the European Association for the Study of the Liver The International Liver Congress 2019 in Vienna, Austria. A4250 is a highly potent and selective inhibitor of the ileal bile acid transporter currently being studied in a Phase 3 clinical trial in children with progressive familial intrahepatic cholestasis, a life-threatening, rare cholestatic liver disease. Albireo plans to initiate a second A4250 pivotal trial, in biliary atresia, in the second half of 2019. The open-label, multicenter, dose-finding Phase 2 clinical trial assessed the safety and tolerability of A4250 in 20 children with cholestatic liver diseases, including PFIC, Alagille syndrome and biliary atresia. Efficacy endpoints included change in serum bile acid levels and pruritus. A4250 was administered orally in doses ranging from 10 microg/kg to 200 microg/kg once daily for 4 weeks. A4250 demonstrated marked sBA reductions of up to 92% in the majority of Alagille patients. The majority of Alagille patients also showed improvement in pruritus as measured by three different scales. One patient had an elevation in bile acids versus baseline. No effect was observed in a third patient with a low baseline sBA. These data, combined with the total dataset of n =24, form the basis for a pivotal development program in a second indication, biliary atresia. In patients with Alagille and biliary atresia, A4250 was generally well-tolerated. Adverse events, including some increased transaminases, were mild and transient. Two Alagille patients with high baseline transaminase levels experienced further increases, which informed the decision to not dose escalate.