Mirum Pharmaceuticals recently announced positive topline results from its phase 3 EXPAND study, evaluating Livmarli (maralixibat) for cholestatic pruritus in patients six months and older with ultra-rare cholestatic liver diseases. Jennifer Vittorio, MD, an EXPAND investigator, an Associate Professor of Pediatrics, and the Medical Director of Pediatric Liver Transplantation at NYU Langone Health, discusses the findings.
Understanding Cholestatic Pruritus
Cholestatic pruritus is an intense, chronic skin itch that occurs when bile acids and other pruritogenic substances in the bloodstream build up due to reduced or blocked bile flow from the liver. It’s a common symptom of ultra-rare cholestatic liver diseases, such as progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS).
Although the primary symptom is a persistent itch, cholestatic pruritus can also cause scratching, irritability, disrupted sleep, fatigue, difficulty concentrating, and impaired school performance. These effects can also extend to parents and other family members, substantially impacting a patient’s quality of life.
Maralixibat is an orally administered, ileal bile acid transporter (IBAT) inhibitor approved by the US Food and Drug Administration (FDA) for treating cholestatic pruritus in two pediatric cholestatic liver diseases – in patients with ALGS three months of age and older, and in patients with PFIC 12 months of age and older.
Maralixibat Improves Itching and Reduces Serum Bile Acids
Topline results from the phase 3 EXPAND study (NCT06553768) were announced on October 12, 2026. EXPAND is a phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of maralixibat, an oral solution in children aged six 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 maralixibat currently isn’t approved.
EXPAND enrolled 52 patients, including 46 pediatric and six adult patients, who were randomized to receive maralixibat or placebo during a 20-week double-blind treatment period. The study met its primary endpoint, demonstrating a statistically significant reduction in cholestatic pruritus compared with placebo, and a substantial reduction in serum bile acids.
More specifically, maralixibat:
Improved cholestatic pruritus: Pediatric patients receiving maralixibat experienced a mean 1.81-point improvement in worst-daily itch severity scores from baseline, compared with a 0.83-point improvement among those receiving placebo. The placebo-adjusted treatment difference was 0.98 points (p=0.0004).
Reduced serum bile acids: Serum bile acid levels decreased by 70.1% from baseline among patients receiving maralixibat, compared with 3.5% among those receiving placebo, representing a 69% treatment effect versus placebo.
Safety Findings and Next Steps
Safety findings were consistent with maralixibat’s previous clinical experience, with no new safety signals identified. Gastrointestinal adverse events were among the reported side effects, with diarrhea occurring in 64% of patients receiving maralixibat compared to 11.1% receiving placebo. Abdominal pain occurred in 20% versus 14.8%, respectively.
Mirum plans to submit a supplemental New Drug Application (sNDA) to the FDA in the first half of 2027 based on the EXPAND results. Dr. Vittorio shared that additional research is needed to assess the durability of treatment response, long-term safety and tolerability, and whether symptom improvement results in better daily functioning or longer native-liver survival.
In Their Own Words
“Our goal is to really recognize cholestatic pruritus earlier, treat it more effectively, improve quality of life, and if possible, help patients maintain their native liver for longer.” – Jennifer Vittorio, MD
For more information, visit: https://www.businesswire.com/news/home/20261012685221/en/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-EXPAND-Study-of-LIVMARLI-maralixibat-in-Ultra-Rare-Cholestatic-Liver-Diseases
To learn more about cholestatic pruritus and other symptoms of rare gastrointestinal diseases, visit: https://checkrare.com/diseases/gastrointestinal-diseases/