Maralixibat
/ Selective ileal bile acid transporter (IBAT/ASBT) inhibitor (small molecule)ALIAS · LIVMARLI (trade) · Maralixibat chloride · SHP-625 · LUM-001
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Tier 1. Maralixibat (LIVMARLI) is a non-systemic, minimally absorbed selective ileal bile acid transporter (IBAT/ASBT) inhibitor. FDA approval 2021 for cholestatic pruritus in patients with Alagille syndrome aged 3 months and older, based on the ICONIC Phase 2 trial. Indication expanded in 2024 to progressive familial intrahepatic cholestasis (PFIC) based on the EMBARK Phase 3 program.
Maralixibat is a selective small-molecule inhibitor of the apical sodium-dependent bile acid transporter (ASBT, also called IBAT), expressed on the luminal surface of terminal ileal enterocytes. Inhibition of intestinal bile acid reabsorption interrupts the enterohepatic circulation, increases faecal bile acid excretion, lowers serum bile acid concentrations, and reduces the cholestatic pruritus burden that defines Alagille syndrome and certain PFIC subtypes. The compound is minimally systemically absorbed; the pharmacology is luminal.
Tier 1. The ICONIC Phase 2 trial (Gonzales and colleagues 2021 with subsequent open-label extension) randomised paediatric Alagille syndrome participants with cholestatic pruritus to maralixibat or placebo and reported reduced pruritus scores and serum bile acids; long-term extension data through five years (Loomes and colleagues, Hepatology 2021) supported durability of effect. The EMBARK Phase 3 trial (Karpen and colleagues, Lancet 2023) extended the evidence base into PFIC.
Common adverse events are gastrointestinal (diarrhoea, abdominal pain) related to the increased luminal bile acid load and altered bile acid pool composition. Liver enzyme elevations and fat-soluble vitamin malabsorption secondary to interrupted bile acid recycling have been reported and require monitoring. Class concerns about long-term effects on enterohepatic bile acid biology in growing children remain under post-marketing surveillance.
Regulatory status
- FDA status:
- FDA-approved
- Compounding:
- Not eligible for compounding (approved, not in shortage)
Maralixibat is one of two IBAT inhibitors approved in this orphan indication space (the other is odevixibat, approved earlier for PFIC). Comparative head-to-head trials between the two have not been performed; cross-trial comparisons are confounded by trial design and population differences. Vendor research-chemical use is not relevant — this is a prescription orphan drug with regulated paediatric administration.