SHP 625 fails Phase II IMAGO trial to treat Alagille syndrome-Shire

Shire plc announced that the 13-week Phase II IMAGO trial of its investigational compound SHP 625 (LUM 001) did not meet the primary or secondary endpoints in the study of 20 pediatric patients with Alagille syndrome (ALGS), a rare, life-threatening genetic disorder that presents with chronic cholestasis (accumulation of bile acids in the liver) and severe pruritus (itching). The primary endpoint was the change from baseline in serum bile acid levels as compared to placebo. The secondary endpoint of pruritus was assessed using the novel ItchRO™ instrument.

Mean serum bile acid levels and pruritus at the end of the study were lower in both SHP 625 and placebo treated groups as compared to baseline. However, in a post-hoc analysis, a positive correlation between percent changes from baseline in serum bile acid levels and pruritis was observed in the SHP 625 treated group. The number of patients in the placebo treated group was too small to make an accurate assessment of this relationship.

In addition to IMAGO, two larger placebo-controlled phase II studies in ALGS are in progress, one of which has pruritus as the primary endpoint. SHP 625 is also being studied in progressive familial intrahepatic cholestasis, primary biliary cirrhosis and primary sclerosing cholangitis.