Mirum’s LIVMARLI met the Phase 3 EXPAND primary endpoint, improving itching and reducing serum bile acids in patients with ultra-rare cholestatic liver diseases
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Mirum Pharmaceuticals reported positive topline results from the Phase 3 EXPAND study evaluating LIVMARLI (maralixibat) in patients aged six months and older with cholestatic pruritus associated with ultra-rare cholestatic liver diseases, including biliary atresia. The randomized, placebo-controlled study met its primary endpoint and achieved statistical significance across all five prespecified secondary endpoints.
The findings support Mirum’s plan to submit a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) in the first half of 2027, seeking to expand LIVMARLI’s use to additional ultra-rare cholestatic liver diseases.
Phase 3 EXPAND Meets Primary Endpoint
EXPAND enrolled 52 patients, including 46 pediatric and six adult participants. Patients received oral maralixibat at 285 µg/kg twice daily or placebo during the 20-week double-blind treatment period.
The primary endpoint assessed the change from baseline in the average worst-daily Itch Reported Outcome (Observer) severity score, known as ItchRO(Obs), during Weeks 13–20. The observer-reported scale ranges from 0 to 4, with lower scores indicating less severe itching.
In the primary analysis population of pediatric patients, itch-severity scores improved by 1.81 points with maralixibat, compared with 0.83 points with placebo. The placebo-adjusted treatment difference was 0.98 points (p=0.0004).
The proportion of days with pruritus improvement reached 86.0% with maralixibat versus 49.1% with placebo, a difference of 36.9 percentage points (p=0.0008). Improvement was defined as a worst-daily ItchRO(Obs) score of 1 or lower, or a reduction of at least one point from baseline.
These results indicate a statistically significant improvement in itching, a key symptom of cholestatic liver disease. The placebo response underscores the importance of evaluating the treatment effect relative to the comparator.
Serum Bile Acids Decline Substantially
Across the overall study population, serum bile acids (sBA) decreased by 70.1% from baseline with maralixibat, compared with 3.5% with placebo. The reported placebo-adjusted treatment effect was 69.0% (p<0.0001).
The analysis used changes from baseline averaged across Weeks 12 and 20. Because the treatment effect was estimated using log-transformed values and back-transformed to the original scale, the 69.0% estimate should not be interpreted as a simple arithmetic difference between the groups.
The concurrent improvements in itching and serum bile acids provide complementary evidence of treatment activity, although biochemical changes should not be equated directly with symptom improvement.
Findings in Biliary Atresia
The prespecified subgroup analysis included 25 patients with biliary atresia and a native liver: 11 received maralixibat and 14 received placebo.
In this subgroup, itch-severity scores improved by 2.16 points with maralixibat and 1.01 points with placebo, yielding a treatment difference of 1.15 points (p=0.0002). The proportion of days with pruritus improvement reached 96.4% versus 52.2%, respectively, a difference of 44.1 percentage points (p=0.0045).
Serum bile acids decreased by 75.5% with maralixibat and 9.0% with placebo. The reported placebo-adjusted treatment effect was 73.1% (p<0.0001).
These findings are particularly relevant because treatment options for biliary atresia-associated cholestatic pruritus remain limited, and LIVMARLI is not currently FDA-approved for this indication. Liver transplantation may be required as the disease progresses, but EXPAND did not evaluate whether maralixibat reduces transplantation requirements. The small subgroup also limits the precision and generalizability of the results.
Safety and Tolerability
The safety profile was consistent with previous clinical experience, with no new safety signals reported. Treatment-emergent adverse events occurred in 96.0% of maralixibat recipients and 96.3% of placebo recipients. Grade 3 or higher events occurred in 24.0% and 22.2%, respectively, while serious adverse events were reported in 20.0% and 18.5%.
Diarrhea was more frequent with maralixibat (64.0% versus 11.1%), as was abdominal pain (20.0% versus 14.8%). Elevated alanine aminotransferase (ALT) occurred in 8.0% of maralixibat recipients (2/25) and 3.7% of placebo recipients (1/27). These small numbers limit interpretation of the difference.
One patient receiving maralixibat discontinued because of a treatment-emergent adverse event, compared with none receiving placebo. One patient in the maralixibat group had an adverse event considered related to study drug; no treatment-related serious adverse events were reported in that group. No treatment-emergent adverse events leading to death were reported.
Regulatory Outlook
LIVMARLI is an orally administered ileal bile acid transporter (IBAT) inhibitor approved in the United States for cholestatic pruritus associated with Alagille syndrome and progressive familial intrahepatic cholestasis in specified age groups.
Mirum’s planned sNDA submission in the first half of 2027 is the next regulatory milestone. Although the topline findings demonstrate statistically significant improvements in itching and serum bile acids, FDA review will determine whether the evidence supports an expanded indication. Further analyses will help characterize the benefit-risk profile across the different disease populations.
References
Mirum Pharmaceuticals Announces Primary Endpoint Met in Phase 3 EXPAND Study of LIVMARLI® (maralixibat) in Ultra-Rare Cholestatic Liver Diseases, Mirum Pharmaceuticals, 12 October 2026
Evaluation of Maralixibat in Pruritus Associated with General Cholestatic Liver Disease (EXPAND), ClinicalTrials.gov ID NCT06553768
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.