FDA notifies providers of safety-related changes to prescribing information of maralixibat, odevixibat | Image Credit: Contemporary Pediatrics

The FDA has updated the prescribing information for the ileal bile acid transporter (IBAT) inhibitors maralixibat (Livmarli; Mirum Pharmaceuticals) and odevixibat (Bylvay; Ipsen), reflecting new safety information related to hepatotoxicity and bleeding. Maralixibat is approved for patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), while odebixibat is approved to treat cholestatic pruritus in patients with ALGS.^1-3

The updated labeling includes a new contraindication for patients with prior or active hepatic events, as well as expanded warnings for bleeding risks associated with fat-soluble vitamin (FSV) deficiency. Both safety updates were prompted by data from ongoing clinical trials and postmarket surveillance.¹

Hepatotoxicity-related changes include recommendations for monitoring liver function and specific guidance for when to discontinue treatment. The FDA noted that additional data have shown more severe hepatic complications, including variceal hemorrhage and hepatic encephalopathy.

"With increased patient exposure through clinical trials and postmarket use, there have been more reports of bleeding," stated the FDA in a press release. "The updated labeling for maralixibat and odevixibat expands on the discussion of bleeding as an adverse reaction in the Warnings and Precautions and in the Adverse Reactions sections," wrote the federal agency.

More on Maralixibat

Maralixibat was originally approved by the FDA in September 2021 for the treatment of cholestatic pruritus in patients aged 1 year and older with ALGS. It was later approved in March 2024 for patients aged 5 years and older with PFIC, and in August 2024, the indication was expanded again to include PFIC patients aged 12 months and older.²

Most recently, on April 14, 2025, the FDA approved a tablet formulation of maralixibat for both ALGS and PFIC patients. This formulation allows for once-daily oral administration and is intended to offer more flexibility for older children and adolescents. The approval was based on findings from the ICONIC and MARCH PFIC trials, which demonstrated improvements in pruritus severity, bile acid levels, bilirubin, and growth outcomes.

At the time of approval, Peter Radovich, president of Mirum Pharmaceuticals, stated that the tablet form “provides a meaningful additional treatment option” for patients and offers a more convenient alternative to the oral solution for those old enough to swallow tablets.

More on Odevixibat

Odevixibat was first approved by the FDA in 2021 for the treatment of cholestatic pruritus in patients with PFIC. On June 15, 2023, it received a label expansion for use in ALGS patients aged 12 months and older.³

The expanded approval was based on results from the phase 3 ASSERT study, which showed a statistically significant improvement in itching severity compared to placebo, measured by the PRUCISION Observer-Reported Outcome scale. The study enrolled patients from 32 global sites and demonstrated meaningful relief from pruritus over 24 weeks.

Click here for more data on odevixibat.

References:

1. Updated labeling for IBAT inhibitors maralixibat and odevixibat related to hepatotoxicity and the fat-soluble vitamin deficiency sequela of bleeding. Press release. FDA. June 27, 2025. Accessed June 30, 2025. https://mjh.sanity.studio/contpeds/structure/article;73ccfbd8-4dbc-41ad-985d-e26fa6bc9536
2. Fitch J. FDA approves maralixibat tablet formulation for ALGS and PFIC. Contemporary Pediatrics. April 14, 2025. Accessed June 30, 2025. https://www.contemporarypediatrics.com/view/fda-approves-maralixibat-tablet-formulation-for-algs-and-pfic
3. FDA approves odevixibat for cholestatic pruritus in ALGS patients. June 15, 2023. Accessed June 30, 2025. https://www.contemporarypediatrics.com/view/fda-approves-odevixibat-for-cholestatic-pruritus-in-algs-patients