The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for maralixibat for the treatment of cholestatic pruritus in patients with Alagille syndrome.

Maralixibat works by inhibiting the apical sodium dependent bile acid transporter. This leads to increased bile acid excretion in the feces and reduced levels of bile acids systemically.

The NDA submission is supported by data from the phase 2b ICONIC study ( NCT02160782) that evaluated the efficacy and safety of maralixibat in patients 1 to 18 years of age with Alagille syndrome. Following 18 weeks of oral maralixibat treatment, study participants were randomly assigned to receive either maralixibat (n=13) or placebo (n=16) for 4 weeks. After the randomized withdrawal period, all patients received maralixibat for the remaining 48 weeks. The coprimary endpoints were the mean change in fasting serum bile acid (sBA) levels during the randomized drug withdrawal period from week 18 to 22, and the proportion of patients with treatment-emergent adverse events (TEAEs). 

Results showed that during the withdrawal period, maralixibat significantly reduced sBA levels (defined as an sBA reduction of ³50%) compared with placebo (P <.05). Moreover, patients treated with maralixibat achieved clinically relevant and statistically significant improvements in key secondary endpoints including itch severity and xanthoma severity. The most common TEAEs reported during the study were diarrhea and abdominal pain.

A Prescription Drug User Fee Act (PDUFA) target date of September 29, 2021 has been set for the application review. 

“With more than 6 years of follow-up data showing durability of response as well as safety, we believe that maralixibat, if approved, would provide a meaningful treatment option that will ultimately reduce the need for liver transplantation,” said Chris Peetz, president and chief executive officer at Mirum Pharmaceuticals.


1.    Mirum Pharmaceuticals announces FDA acceptance of New Drug Application and Priority Review for maralixibat in Alagille syndrome. [press release]. Foster City, CA: Mirum Pharmaceuticals, Inc.; March 29, 2021. 

2.    Mirum Pharmaceuticals presents new data demonstrating durable improvements in clinical outcome measures in patients with PFIC2 and Alagille syndrome treated with maralixibat. [press release]. Foster City, CA: Mirum Pharmaceuticals, Inc.; April 15, 2019.