Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study

Hepatol Commun. 2022 Sep;6(9):2379-2390. doi: 10.1002/hep4.1980. Epub 2022 May 4.


Children with progressive familial intrahepatic cholestasis, including bile salt export pump (BSEP) and familial intrahepatic cholestasis-associated protein 1 (FIC1) deficiencies, suffer debilitating cholestatic pruritus that adversely affects growth and quality of life (QoL). Reliance on surgical interventions, including liver transplantation, highlights the unmet therapeutic need. INDIGO was an open-label, Phase 2, international, long-term study to assess the efficacy and safety of maralixibat in children with FIC1 or BSEP deficiencies. Thirty-three patients, ranging from 12 months to 18 years of age, were enrolled. Eight had FIC1 deficiency and 25 had BSEP deficiency. Of the latter, 6 had biallelic, protein truncating mutations (t)-BSEP, and 19 had ≥ 1 nontruncating mutation (nt)-BSEP. Patients received maralixibat 266 μg/kg orally, once daily, from baseline to Week 72, with twice-daily dosing permitted from Week 72. Long-term efficacy was determined at Week 240. Serum bile acid (sBA) response (reduction in sBAs of > 75% from baseline or concentrations <102.0 μmol/L) was achieved in 7 patients with nt-BSEP, 6 during once-daily dosing, and 1 after switching to twice-daily dosing. sBA responders also demonstrated marked reductions in sBAs and pruritus, and increases in height, weight, and QoL. All sBA responders remained liver transplant-free after > 5 years. No patients with FIC1 deficiency or t-BSEP deficiency met the sBA responder criteria during the study. Maralixibat was generally well-tolerated throughout the study. Conclusion: Response to maralixibat was dependent on progressive familial intrahepatic cholestasis subtype, and 6 of 19 patients with nt-BSEP experienced rapid and sustained reductions in sBA levels. The 7 responders survived with native liver and experienced clinically significant reductions in pruritus and meaningful improvements in growth and QoL. Maralixibat may represent a well-tolerated alternative to surgical intervention.

Trial registration: NCT02057718.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters
  • Bile Acids and Salts
  • Child
  • Cholestasis* / genetics
  • Cholestasis, Intrahepatic* / drug therapy
  • Humans
  • Pruritus / drug therapy
  • Quality of Life


  • ATP-Binding Cassette Transporters
  • Bile Acids and Salts

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 1

Associated data