Foster City, California, United States, October 12, 2026
Mirum Pharmaceuticals, Inc. has announced positive topline results from its Phase 3 EXPAND clinical trial evaluating LIVMARLI® (maralixibat) for cholestatic pruritus in patients with ultra-rare cholestatic liver diseases, including biliary atresia. The study met its primary endpoint, demonstrating a statistically significant reduction in itching compared with placebo, while also achieving statistical significance across all five prespecified secondary endpoints. The findings could support the potential expansion of maralixibat into additional rare liver disease populations, where treatment options for persistent itching remain limited. According to the company’s October 12, 2026 announcement, Mirum plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration in the first half of 2027, based on the EXPAND results.
Phase 3 EXPAND Trial Demonstrates Significant Itching Relief
The Phase 3 EXPAND study evaluated maralixibat in 52 patients, including 46 pediatric and six adult participants, with ultra-rare cholestatic liver diseases. During the 20-week double-blind treatment period, participants received either maralixibat at a dose of 285 micrograms per kilogram twice daily or placebo. The primary endpoint measured the change from baseline in the average worst-daily itching severity score during Weeks 13–20, using the observer-reported Itch Reported Outcome (ItchRO[Obs]) assessment. Among pediatric patients in the primary analysis population, maralixibat produced a mean 1.81-point improvement in itching severity, compared with a 0.83-point improvement among those receiving placebo. This represented a placebo-adjusted treatment difference of 0.98 points, achieving statistical significance with a p-value of 0.0004. The results suggest that maralixibat may provide meaningful relief from cholestatic pruritus, a distressing symptom that can interfere with sleep, daily activities and quality of life for affected children and families.
Serum Bile Acids and Biliary Atresia Results
Beyond the primary endpoint, EXPAND demonstrated substantial reductions in serum bile acid levels, another important measure in cholestatic liver diseases. Patients receiving maralixibat experienced a 70.1% reduction from baseline in serum bile acids, compared with a 3.5% reduction in the placebo group. The estimated treatment effect versus placebo was 69.0%, with a p-value below 0.0001. The company also reported positive results in the subgroup of patients with biliary atresia and a native liver. In this subgroup, itching severity improved by a mean of 2.16 points with maralixibat, compared with 1.01 points with placebo, representing a statistically significant treatment difference of 1.15 points (p=0.0002). Serum bile acids declined by 75.5% from baseline in the maralixibat group, compared with 9.0% in the placebo group. Additionally, the percentage of days with itching improvement reached 96.4% among maralixibat-treated patients in this subgroup, versus 52.2% with placebo. All five prespecified secondary endpoints achieved statistical significance, including the three endpoints evaluated in patients with biliary atresia and a native liver.
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Safety Profile and Planned Regulatory Submission
According to Mirum Pharmaceuticals, the safety findings from EXPAND were consistent with previous clinical experience with maralixibat, and no new safety signals were observed during the 20-week double-blind period. Treatment-emergent adverse events were reported in 96.0% of participants receiving maralixibat and 96.3% of those receiving placebo. Diarrhea was more frequent in the maralixibat group, occurring in 64.0% of patients compared with 11.1% in the placebo group. These findings underscore the importance of continued safety monitoring as clinical development progresses. LIVMARLI is an orally administered ileal bile acid transporter (IBAT) inhibitor already approved in the United States for cholestatic pruritus associated with Alagille syndrome in eligible pediatric patients and progressive familial intrahepatic cholestasis in eligible patients. However, its use for the additional ultra-rare conditions studied in EXPAND is not currently approved. The company intends to use the new findings to support a U.S. supplemental regulatory submission in the first half of 2027. The planned filing remains subject to regulatory requirements, and further review will determine whether the medicine can be made available for these additional patient populations.
The EXPAND findings represent an important clinical development milestone for rare liver disease research. Persistent cholestatic itching can create substantial challenges for patients and caregivers, particularly when available treatment options are limited. By demonstrating statistically significant improvements in itching severity and serum bile acid levels, maralixibat has shown potential to address an important unmet medical need. Further regulatory review and continued clinical evaluation will be necessary to establish its role in additional ultra-rare cholestatic liver diseases.
Source: Mirum Pharmaceuticals press release
