Maralixibat Eases Cholestatic Pruritus in Phase 3 EXPAND Trial

Maralixibat (Livmarli) significantly reduced cholestatic pruritus vs placebo in the phase 3 EXPAND trial, which enrolled patients aged ≥6 months with ultra-rare cholestatic liver diseases, including biliary atresia.¹ The trial met its primary endpoint and all 5 prespecified secondary endpoints, including the 3 assessed in patients with biliary atresia and a native liver.

In the primary analysis population of pediatric patients, maralixibat produced a placebo-adjusted 0.98-point improvement in average worst daily itch severity during weeks 13 to 20 (P = .0004). Serum bile acids fell 69.0% vs placebo across the overall population (P < .0001).¹

“The magnitude and consistency of improvements in pruritus and serum bile acid levels observed in EXPAND are compelling, including for patients with biliary atresia,” Jennifer Vittorio, MD, FAASLD, associate professor of pediatrics and medical director of pediatric liver transplantation at NYU Langone Health, said in a statement.

EXPAND Phase 3 Trial Design and Patient Population

EXPAND is a randomized, double-blind, placebo-controlled trial evaluating maralixibat oral solution in children and adults with cholestatic pruritus associated with ultra-rare cholestatic liver diseases for which the drug is not currently approved.¹

The trial enrolled 52 patients, including 46 pediatric and 6 adult patients. Participants were randomized to maralixibat 285 µg/kg twice daily or placebo for a 20-week double-blind period.

The primary endpoint was change from baseline in average worst daily Itch Reported Outcome (Observer) (ItchRO[Obs]) severity score, a 0 to 4 scale, during weeks 13 to 20. Secondary endpoints included change in serum bile acids, the percentage of days with pruritus improvement, and corresponding prespecified analyses in patients with biliary atresia and a native liver.

Maralixibat Pruritus and Serum Bile Acid Results

Among pediatric patients, mean ItchRO(Obs) severity scores improved by 1.81 points with maralixibat (n = 22) vs 0.83 points with placebo (n = 24). Patients receiving maralixibat had pruritus improvement on 86.0% of days vs 49.1% with placebo, a difference of 36.9 percentage points (P = .0008).¹ Improvement was defined as a worst daily score ≤1 or a decrease of ≥1 point from baseline.

Across the overall population, serum bile acids decreased 70.1% from baseline with maralixibat (n = 25) vs 3.5% with placebo (n = 27).

Maralixibat Reduces Pruritus in Biliary Atresia Subgroup

In patients with biliary atresia and a native liver, maralixibat improved ItchRO(Obs) severity scores by 2.16 points (n = 11) vs 1.01 points with placebo (n = 14), a placebo-adjusted difference of 1.15 points (P = .0002).¹

Pruritus improvement occurred on 96.4% of days with maralixibat vs 52.2% with placebo (P = .0045). Serum bile acids fell 75.5% vs 9.0%, corresponding to a 73.1% treatment effect (P < .0001).

Maralixibat Safety Profile in EXPAND: Diarrhea Most Common Adverse Event

Treatment-emergent adverse events (TEAEs) occurred in 96.0% of patients receiving maralixibat and 96.3% receiving placebo. Grade ≥3 TEAEs were reported in 24.0% and 22.2%, respectively, and serious TEAEs in 20.0% and 18.5%.¹

Diarrhea was the most common TEAE of interest, reported in 64.0% of the maralixibat group vs 11.1% of the placebo group. Abdominal pain occurred in 20.0% vs 14.8%, and increased alanine aminotransferase in 8.0% vs 3.7%.

One patient receiving maralixibat discontinued because of a TEAE, and no deaths occurred. None of the serious adverse events in the maralixibat group were considered treatment related.

IBAT Inhibitor Trials in Biliary Atresia: EMBARK and BOLD

Biliary atresia is the leading cause of liver-related death in children and the most common indication for pediatric liver transplantation.⁴ EXPAND follows 2 earlier IBAT inhibitor trials in the disease, both of which evaluated treatment after Kasai hepatoportoenterostomy.

The phase 2 EMBARK trial evaluated maralixibat as an adjuvant to Kasai surgery and did not meet its primary endpoint of mean change in bilirubin at week 26 or its key secondary endpoints.² In July 2026, Ipsen reported that the phase 3 BOLD trial of odevixibat (Bylvay), which enrolled 254 infants, did not improve native liver survival vs placebo.³

Unlike those trials, EXPAND assessed maralixibat for cholestatic pruritus rather than disease progression.

Maralixibat sNDA Planned for Ultra-Rare Cholestatic Liver Diseases

Maralixibat is an oral IBAT inhibitor that blocks bile acid reuptake in the intestine. The US Food and Drug Administration (FDA) first approved it in September 2021 for cholestatic pruritus in Alagille syndrome. The label now covers patients aged ≥3 months.

The FDA approved maralixibat for progressive familial intrahepatic cholestasis in March 2024 and expanded that indication to patients aged ≥12 months in July 2024. A tablet formulation followed in April 2025.

Mirum plans to submit a supplemental new drug application (sNDA) to the FDA in the first half of 2027 based on the EXPAND results.¹ The findings are topline and have not yet been published in a peer-reviewed journal.

“For families living with ultra-rare cholestatic liver diseases, the possibility of new treatment options brings tremendous hope,” Jen Lau, MPH, cofounder and executive director of Biliary Atresia Research and Education (BARE), said in a statement.

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 12, 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. Mirum Pharmaceuticals announces data from EMBARK phase 2b study for biliary atresia. News release. Mirum Pharmaceuticals. December 18, 2023. Accessed October 12, 2026. https://www.businesswire.com/news/home/20231218379840/en/

3. Ipsen provides update on phase III BOLD trial in biliary atresia. News release. Ipsen. July 24, 2026. Accessed October 12, 2026. https://www.ipsen.com/press-release/ipsen-provides-update-on-phase-iii-bold-trial-in-biliary-atresia-3332691/

4. 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