Maralixibat is a novel, minimally absorbed, orally administered investigational medication being evaluated in several rare cholestatic liver diseases. Maralixibat inhibits the apical sodium-dependent bile acid transporter (ASBT), resulting in more bile acids being excreted in the feces, leading to lower levels of bile acids systemically, thereby potentially reducing bile acid-mediated liver damage and related effects and complications. Maralixibat has data spanning more than six years of clinical evaluation in patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC).
In the ICONIC Phase 2b ALGS clinical trial, patients receiving maralixibat experienced significant reductions in bile acids and pruritus compared to placebo, as well as improvements in quality of life, xanthomas and accelerated growth long-term.
In the Phase 2 INDIGO study for PFIC, patients with PFIC2 (a genetically defined subset of PFIC also known as bile salt export pump deficiency), who achieved serum bile acid control during a five-year analysis were shown to have significant improvement in transplant-free survival. Patients who responded to maralixibat also experienced improvements across multiple parameters including normalization of liver enzyme and bilirubin levels, decreased pruritus, and improvements in growth.
The most frequent treatment-related adverse events were diarrhea and abdominal pain.
Until maralixibat is approved and available for prescribing, the medication can be provided to eligible patients with ALGS through Mirum’s expanded access program (EAP). For more information, please visit ALGSEAP.com. To learn more about the Phase 3 MARCH PFIC clinical trial, visit the study website at PFICtrial.com. For more information about the Phase 2 EMBARK study, visit clinicaltrials.gov.
The U.S. Food and Drug Administration has granted maralixibat Breakthrough Therapy designation for the treatment of pruritus associated with ALGS one year of age and older and for the treatment of PFIC2. Orphan Drug Designation was also granted to maralixibat for the treatment of patients with PFIC, ALGS and biliary atresia in the United States.