Mechanism of Action (MOA) for the First and Only FDA-Approved Treatment for Cholestatic Pruritus in Alagille Syndrome1
Mechanism of Disease (MOD)
Bile Acid Buildup in Alagille Syndrome






Normally, adequate enterohepatic circulation is crucial for homeostatic maintenance of the body’s bile acid pool.2
- This process starts with bile acid synthesis in hepatocytes and its subsequent biliary secretion, primarily mediated by the bile salt export pump2
- Bile acids then move through bile ducts to the gallbladder for storage2
- Later, bile acids are released into the small intestine to aid in lipid digestion and absorption2

Per cycle, approximately 95% of bile acids are reabsorbed from the terminal ileal lumen…
…by the ileal bile acid transporter (IBAT) for return to the liver through the hepatic portal vein.2

Bile acids that are not reabsorbed from the intestine via the IBAT are lost in feces…
…and, under steady-state conditions, are replaced by hepatic de novo synthesis.2

In cholestatic liver disease, bile flow is impaired between the liver and the duodenum, leading to a buildup of bile acids in the liver.3,4
There is also spillover of bile acids into the bloodstream, resulting in an increase in serum bile acids (sBA) systemically.3,4

In Alagille syndrome, bile ducts are narrow, malformed, and/or reduced in number.2,5
This results in bile acid buildup in the liver and bloodstream.2,5
Related to elevated serum bile acid (sBA) levels, cholestatic pruritus in Alagille syndrome is among the worst of any cholestatic liver disease.2,6-8


Mechanism of Action
LIVMARLI Helps Battle Bile Acid Buildup




LIVMARLI is an ileal bile acid transporter (IBAT) inhibitor and the first and only approved treatment for cholestatic pruritus in patients with Alagille syndrome who are ≥1 year old.1

LIVMARLI interrupts recirculation of bile acids to the liver and increases fecal excretion of bile acids to reduce serum bile acid (sBA) levels in the body, with minimal systemic absorption.1,9,10

Although the complete mechanism by which LIVMARLI improves cholestatic pruritus in patients with Alagille syndrome is unknown, it may involve inhibition of the ileal bile acid transporter (IBAT), which results in decreased reuptake of bile salts, as observed by a decrease in sBA.1
- In the ICONIC study, sBA reductions correlated with reductions in cholestatic pruritus intensity, further supporting the potential causal relationship between the two11
During the first year of treatment, 83% (n=24/29) of patients with Alagille syndrome experienced a ≥20% reduction in sBA levels vs baseline with LIVMARLI.9,12
Outmatch
the Scratch
Significant improvements in cholestatic pruritus from baseline were achieved as early as Week 3 and maintained through 1 year in patients with Alagille syndrome taking LIVMARLI (P<0.0001).9,13
See the Efficacy Data
Encourage patients to download the Itch✓ app to help them track symptom patterns over time and generate customized reports to share at appointments.
Check Out the Itch✓ AppMAP assists both you and your patients at every turn, helping you navigate the payer approval process—and beyond—with ease.
Learn More About MAP