Primary Endpoint Met in Phase 3 EXPAND Study of LIVMARLI in Ultra-Rare Cholestatic Liver Diseases – Mirum
Mirum Pharmaceuticals, Inc. announced topline results from the Phase 3 EXPAND study evaluating LIVMARLI (maralixibat) for the treatment of cholestatic pruritus in patients aged 6 months or older with ultra-rare cholestatic liver diseases, including biliary atresia.
The study met its primary endpoint and achieved statistical significance across all five prespecified secondary endpoints, including the three endpoints in patients with biliary atresia and a native liver.
The Phase 3 EXPAND study enrolled 52 patients, including 46 pediatric and six adult patients, who were randomized during the 20-week double-blind period to treatment with maralixibat 285 µg/kg twice daily (BID) or placebo. Treatment with maralixibat demonstrated a statistically significant improvement in pruritus compared with placebo in the primary analysis population of pediatric patients. Maralixibat resulted in a mean 1.81-point improvement from baseline in average worst-daily ItchRO(Obs) severity score during Weeks 13-20 compared with a 0.83-point improvement for placebo, corresponding to a placebo-adjusted treatment difference of 0.98 points (p=0.0004). Maralixibat also resulted in a 70.1% reduction from baseline in serum bile acids (sBA), compared with 3.5% for placebo, corresponding to a 69.0% treatment effect versus placebo (p<0.0001).
Safety findings in EXPAND were consistent with prior clinical experience with maralixibat and no new safety signals were observed.
“These results are especially important because patients with ultra-rare cholestatic liver diseases continue to face a significant burden from pruritus,” said Rob Myers, M.D., Chief Medical Officer at Mirum Pharmaceuticals. “The improvements in pruritus and reductions in serum bile acids observed in EXPAND reinforce the potential for maralixibat to address this unmet need and benefit a broader population of patients living with ultra-rare cholestatic liver diseases.”
“Cholestatic pruritus can be relentless and profoundly disruptive for people living with ultra-rare cholestatic liver diseases, yet treatment options remain limited,” said Jennifer Vittorio, M.D., FAASLD, Associate Professor of Pediatrics and Medical Director, Pediatric Liver Transplantation, NYU Langone Health. “The magnitude and consistency of improvements in pruritus and serum bile acid levels observed in EXPAND are compelling, including for patients with biliary atresia.”
“For families living with ultra-rare cholestatic liver diseases, the possibility of new treatment options brings tremendous hope,” said Jen Lau, MPH, Co-Founder and Executive Director of BARE, Inc. (Biliary Atresia Research and Education). “These results are meaningful for the biliary atresia community, where children and families continue to face significant challenges due to cholestatic pruritus. We are deeply grateful to the patients and families who participated in EXPAND and helped move this research forward.”
Mirum plans to submit a supplemental New Drug Application (sNDA) in the United States in the first half of 2027 based on EXPAND results.
About the EXPAND Phase 3 Study
EXPAND is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of LIVMARLI (maralixibat) oral solution in children aged 6 months and older and adults with cholestatic pruritus associated with ultra-rare cholestatic liver diseases. These diseases include biliary atresia and other rare conditions for which LIVMARLI is not currently approved. The primary endpoint is change from baseline in average worst-daily ItchRO(Obs) severity score during Weeks 13-20. Secondary efficacy measures include changes in serum bile acid levels and days with pruritus improvement, with corresponding prespecified analyses of pruritus severity, serum bile acids and days with pruritus improvement in patients with biliary atresia and a native liver.
