Real-world experience of maralixibat in Alagille syndrome: Novel findings outside of clinical trials

ObjectiveMaralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged >= 3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS.MethodsWe reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation.ResultsMaralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin.ConclusionMaralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported. What is Known Maralixibat is approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome aged >= 3 months. Studies of maralixibat utilized strict inclusion/exclusion criteria to best ascertain effectiveness and safety.What is New Since clinical trials completion, patients have received maralixibat through an expanded access program or commercial approval. Maralixibat appeared effective and well tolerated in patients who would have been excluded from clinical trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, medication administration through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation.