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.