Maralixibat Reduces Cholestatic Pruritus in Phase 3 EXPAND, With Jennifer Vittorio, MD

Maralixibat (Livmarli), an oral ileal bile acid transporter (IBAT) inhibitor, significantly reduced cholestatic pruritus compared with placebo in the phase 3 EXPAND trial, including among patients with biliary atresia. In the pediatric primary analysis population, the treatment produced a placebo-adjusted 0.98-point improvement in itch severity (P = .0004), while serum bile acids decreased by 69% relative to placebo across the overall study population.¹

In an interview with HCPLive, Jennifer Vittorio, MD, associate professor of pediatrics and medical director of pediatric liver transplantation at NYU Langone Health, explained the rationale for IBAT inhibition and discussed the design and findings of the phase 3 EXPAND trial.

“A meaningful reduction in pruritus, which is what the study demonstrated, really can translate into better sleep, improved daytime functioning, better quality of life for the whole family,” Vittorio said.

What Is Cholestasis and How IBAT Inhibition Works

Vittorio described cholestasis as an impairment in bile production or flow from the liver to the intestine, resulting in the accumulation of bile acids in the liver and bloodstream. Elevated bile acids are associated with cholestatic pruritus, although the mechanisms underlying itch are multifactorial.

Under normal conditions, bile acids reaching the intestine are largely reabsorbed in the distal ileum through IBAT and returned to the liver. Maralixibat reversibly inhibits IBAT, reducing intestinal bile acid reabsorption and increasing fecal bile acid excretion. This mechanism can lower circulating bile acid concentrations.²

By reducing enterohepatic bile acid recirculation, IBAT inhibition offers a potential approach to managing cholestatic pruritus, although the relationship between circulating bile acid concentrations and itch severity is not fully understood.

EXPAND Trial Design and the ItchRO(Obs) Scale

The phase 3 EXPAND trial enrolled 52 patients, including 46 pediatric and 6 adult patients, with ultra-rare cholestatic liver diseases for which maralixibat is not currently approved. Participants were randomized to maralixibat 285 µg/kg twice daily or placebo during a 20-week double-blind treatment period.¹

Vittorio explained that eligibility required significant cholestatic pruritus alongside biochemical evidence of cholestasis, such as elevated serum bile acids.

The primary endpoint was the change in average worst daily Itch Reported Outcome (Observer) (ItchRO[Obs]) severity score during weeks 13 through 20. The caregiver-reported measure assesses itch severity on a scale from 0, indicating no itch, to 4, indicating debilitating itch.

“The itch reported outcome is a validated tool that’s been used to assess pruritus in cholestatic liver diseases, and the observer reported version, which is the ItchRO(Obs), I think is particularly valuable because young children may not be able to reliably describe their symptoms,” Vittorio said. “This is where the caretakers come in.”

The observer-reported endpoint allows caregivers to document symptoms that young children may be unable to communicate directly, providing a measure of pruritus severity in a population where patient-reported assessments may not be feasible.

Maralixibat Pruritus and Serum Bile Acid Results

In the pediatric primary analysis population, average worst daily ItchRO(Obs) scores improved by 1.81 points with maralixibat compared with 0.83 points with placebo, yielding a placebo-adjusted difference of 0.98 points (P = .0004).¹

Pruritus improvement was reported on 86.0% of days in the maralixibat group compared with 49.1% in the placebo group (P = .0008). Across the overall study population, serum bile acids decreased by 69.0% relative to placebo (P < .0001).¹

Vittorio noted that EXPAND demonstrated reductions in both serum bile acids and pruritus severity, findings consistent with the proposed therapeutic rationale for IBAT inhibition in cholestatic liver disease.

The findings were announced as topline results by Mirum Pharmaceuticals on October 12, 2026, and have not yet been published in a peer-reviewed journal.¹

Maralixibat in Biliary Atresia After EMBARK and BOLD

Biliary atresia is a major cause of pediatric liver-related mortality and the most common indication for liver transplantation in children.³ EXPAND included patients with biliary atresia who retained their native liver, allowing investigators to assess whether IBAT inhibition could alleviate pruritus in this population.

Among these patients, maralixibat was associated with a placebo-adjusted 1.15-point improvement in itch severity (P = .0002). Serum bile acids decreased by 75.5% in the maralixibat group compared with 9.0% in the placebo group.¹

Earlier IBAT inhibitor trials in biliary atresia evaluated whether treatment could influence disease progression following Kasai hepatoportoenterostomy. The phase 2 EMBARK trial of maralixibat did not meet its primary endpoint,⁴ while the phase 3 BOLD trial of odevixibat (Bylvay) did not demonstrate improved native liver survival.⁵

EXPAND addressed a different clinical question, evaluating whether IBAT inhibition could reduce cholestatic pruritus in patients with biliary atresia and other ultra-rare cholestatic liver diseases. Although its findings support a potential symptomatic benefit, they do not establish whether maralixibat alters disease progression or reduces the need for liver transplantation.

Editor’s Note: Disclosures for Jennifer Vittorio, MD, include Mirum Pharmaceuticals.

References

1. Mirum Pharmaceuticals announces primary endpoint met in phase 3 EXPAND study of Livmarli (maralixibat) in ultra-rare cholestatic liver diseases. News release. Mirum Pharmaceuticals. October 12, 2026. Accessed October 16, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-EXPAND-Study-of-LIVMARLI-maralixibat-in-Ultra-Rare-Cholestatic-Liver-Diseases/default.aspx

2. Livmarli (maralixibat). Prescribing information. Mirum Pharmaceuticals. Accessed October 16, 2026. https://files.mirumpharma.com/livmarli/livmarli-prescribinginformation.pdf

3. Schreiber RA, Harpavat S, Hulscher JBF, Wildhaber BE. Biliary atresia in 2021: epidemiology, screening and public policy. J Clin Med. 2022;11(4):999. doi:10.3390/jcm11040999

4. Mirum Pharmaceuticals announces data from EMBARK phase 2b study for biliary atresia. News release. Mirum Pharmaceuticals. December 18, 2023. Accessed October 16, 2026. https://www.businesswire.com/news/home/20231218379840/en/

5. Ipsen provides update on phase III BOLD trial in biliary atresia. News release. Ipsen. July 24, 2026. Accessed October 16, 2026. https://www.ipsen.com/press-release/ipsen-provides-update-on-phase-iii-bold-trial-in-biliary-atresia-3332691/