Maralixibat is a novel, oral, minimally-absorbed therapy being evaluated as a treatment for children with rare cholestatic liver diseases, including Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC). Both of these cholestatic diseases involve an interruption in the flow of bile acid from the liver, resulting in excess bile acid in the liver and systemically. This leads to liver disease and a variety of severe and life-altering symptoms, including stunted growth and chronic and severe itch. Maralixibat works by inhibiting an important carrier protein known as the apical sodium dependent bile acid transporter (ASBT), thereby reducing systemic levels of bile acids.
Maralixibat is currently being evaluated in the Phase 3 MARCH-PFIC Study in children with PFIC, and Mirum is in discussion with regulatory agencies with regard to bringing a much needed solution to children with ALGS. Mirum also is exploring maralixibat as a treatment for other cholestatic liver diseases including biliary atresia with potential plans to initiate a clinical program in 2020.
In the Phase 2 INDIGO clinical trial of maralixibat, children with PFIC2 experienced a multi-parameter response, including reduced pruritus, reductions in serum bile acids, normalization of liver enzymes and improved quality of life scores. A long-term analysis of the INDIGO clinical trial showed an improvement in growth for those patients who had a significant response in sBA and pruritus. Maralixibat has breakthrough therapy designation for the treatment of PFIC2.
In the Phase 2b ICONIC clinical trial of maralixibat in ALGS, children taking maralixibat had statistically significant reductions in pruritus and serum bile acids compared to placebo. At the 48-week measurement, pruritus and serum bile acid reductions were maintained and improvements in xanthomas (disfiguring and often debilitating buildup of lipid deposits) and quality of life were also observed. The FDA has granted maralixibat breakthrough therapy designation for pruritus associated with Alagille syndrome in patients one year of age and older.