IBAT Inhibitors in Pediatric Cholestatic Liver Disease, with Mercedes Martinez, MD

Pruritus is a distressing and often debilitating symptom of pediatric cholestatic liver disease, significantly impacting both affected children and their families.

Typically seen in children with Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), the severity of pruritus can vary from patient to patient—while some children experience mild discomfort, others scratch to the point of skin damage, bleeding, and severe sleep disturbances.

The field of hepatology has seen several recent advancements in pharmacologic therapies for advancing pruritus in both conditions with the advent of ileal bile acid transporter (IBAT) inhibitors. In 2021, the FDA approved odevixibat (Bylvay) for the treatment of pruritus in patients ≥ 3 months of age with PFIC and maralixibat (Livmarli) oral solution for the treatment of cholestatic pruritus in patients with Alagille syndrome ≥ 1 year of age.1,2

In 2023, odevixibat gained an additional indication for cholestatic pruritus in patients ≥12 months of age with Alagille syndrome. A year later, maralixibat was approved for the treatment of cholestatic pruritus in patients ≥ 5 years of age with PFIC.3,4

“For now, they are approved in pediatric populations only, for progressive familial intrahepatic cholestasis, PFIC, and for Allagile syndrome, but we know that they work in other conditions,” said Mercedes Martinez, MD, a professor of pediatrics and medicine, medical director of the intestinal transplant program at the Center for Liver Disease and Abdominal Organ Transplantation, and medical director of the pediatric abdominal organ transplantation program at NewYork-Presbyterian.

Specifically, she referenced clinical trials exploring the use of IBAT inhibitors in adults and pediatric patients with primary sclerosing cholangitis (PSC).

“These really are miracle drugs for this population of patients who have been suffering for years from these symptoms that nobody sees,” Martinez explained. “It's very difficult when you feel so terrible and nobody can see how sick you are or how terrible you feel."

She went on to commend the pharmaceutical industry for focusing on developing treatment for a condition that affects such a small number of patients, noting that these drugs may not be used by millions of people, but saying they will have a significant impact on affected patients’ quality of life and potentially even prevent liver transplantation.

Editors’ note: Martinez has no relevant disclosures.

References

1. Walter K. FDA Approves Odevixibat for PFIC. HCPLive. July 20, 2021. Accessed March 25, 2025. https://www.hcplive.com/view/fda-approves-odevixibat-pfic

2. Walter K. FDA Approves First Treatment for Rare Pediatric Liver Disease. HCPLive. September 29, 2021. Accessed March 25, 2025. https://www.hcplive.com/view/fda-approves-first-treatment-rare-pediatric-liver-disease

3. Kunzmann K. FDA Approves Odevixibat for Cholestatic Pruritus in Alagille Syndrome. HCPLive. June 13, 2023. Accessed March 25, 2025. https://www.hcplive.com/view/fda-approves-odevixibat-cholestatic-pruritus-alagille-syndrome

4. Brooks A. FDA Approval of Maralixibat for Cholestatic Pruritus in PFIC Signals New Frontier for IBAT Inhibitor. HCPLive. March 13, 2024. Accessed March 25, 2025. https://www.hcplive.com/view/fda-approval-of-maralixibat-for-pfic-ibat-inhibitors