Optimizing Cholestatic Disease Care With IBAT Inhibitors, With Mercedes Martinez, MD

As the treatment landscape for rare cholestatic liver diseases evolves, focus is shifting beyond biochemical control to the broader burden of disease. With the emergence of ileal bile acid transporter (IBAT) inhibitors, clinicians are beginning to rethink traditional treatment approaches and their potential to improve both symptoms and long-term outcomes.

In 2025, maralixibat (Livmarli) was granted US Food and Drug Administration (FDA) approval for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC). Most recently, the FDA approved linerixibat (Lynavoy), another IBAT inhibitor, for the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis (PBC). Now, the class of agents is being explored in other rare cholestatic liver diseases in the phase 3 EXPAND trial.

Clinical trials of IBAT inhibitors have primarily focused on pruritus reduction as a primary endpoint, but Mercedes Martinez, MD, a professor of pediatrics and medicine at CUMC, pointed to growing evidence suggesting broader clinical impact. Drawing from registry data and observational cohorts, she noted that patients treated with these agents appear to experience improved native liver survival, reduced need for transplantation, and better nutritional status.

Although the precise mechanisms remain under investigation, she explained that reducing bile acid recirculation likely mitigates hepatotoxicity, while relief from severe pruritus may improve sleep, appetite, and growth.

For Martinez, however, the most striking impact is seen in quality of life. She described dramatic transformations in pediatric patients whose lives had previously been dominated by relentless itching. The downstream effects, including better sleep, improved school performance, and reduced caregiver burden, underscore how profoundly pruritus can shape daily life for both patients and families.

“These kids come to the office, and the skin is like leather [because of how] much they scratch. And now, seeing these kids coming to the office, the skin is very smooth. They are happier, they are doing better in school, because they can focus,” Martinez explained. “It just goes beyond the itch.”

This evolving understanding is also influencing her treatment approach. Traditionally, management of cholestatic pruritus has followed a stepwise paradigm, beginning with antihistamines or bile acid sequestrants and escalating to agents like rifampin. However, Martinez said she now questions that framework. Given the limited efficacy and frequent side effects of older therapies, she believes IBAT inhibitors may warrant earlier use. In her own practice, she has already begun shifting toward these agents as frontline therapy in conditions like PFIC and Alagille syndrome, tailoring dosing based on symptom severity and response.

Despite the promise, Martinez acknowledged ongoing challenges, particularly around access and cost. She stressed that studies like Mirum Pharmaceuticals’ EXPAND study of maralixibat, though limited in size, provide important proof of concept for broader application across cholestatic liver diseases.

Looking ahead, she expressed hope that regulators and payers will recognize the value of these therapies, not only in reducing symptoms, but in meaningfully improving long-term outcomes and quality of life for patients with rare liver diseases.

Editors’ Note: Martinez reports no relevant disclosures.

References

1. Brooks A. FDA Approves Maralixibat (Livmarli) Tablet for Alagille Syndrome, PFIC. HCPLive. April 14, 2025. Accessed April 10, 2026. https://www.hcplive.com/view/fda-approves-maralixibat-livmarli-tablet-alagille-syndrome-pfic

2. Brooks A. FDA Approves Linerixibat (Lynavoy) As First Treatment for Cholestatic Pruritus in PBC. HCPLive. March 19, 2026. Accessed April 10, 2026. https://www.hcplive.com/view/fda-approves-linerixibat-lynavoy-as-first-treatment-for-cholestatic-pruritus-in-pbc

3. Mirum Pharmaceuticals. Mirum Pharmaceuticals Completes Enrollment in Phase 3 EXPAND Study of LIVMARLI® (maralixibat) in Additional Rare Cholestatic Liver Diseases. March 16, 2026. Accessed April 10, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Completes-Enrollment-in-Phase-3-EXPAND-Study-of-LIVMARLI-maralixibat-in-Additional-Rare-Cholestatic-Liver-Diseases/default.aspx