New data suggest that the medication maralixibat, marketed as Livmarli by Mirum Pharmaceuticals, continues to provide significant benefits for children with Alagille syndrome over a period of seven years. The findings, presented at the European Association for the Study of the Liver (EASL) annual congress in June 2024, indicate sustained improvements in itching, liver health markers and growth among young patients receiving the treatment.
Understanding Alagille Syndrome and Cholestatic Pruritus
Alagille syndrome is a rare genetic disorder that primarily affects the liver, heart, and other organs. A key characteristic of the condition is a deficiency in bile ducts, the small tubes that carry bile from the liver to the small intestine. This deficiency leads to a buildup of bile in the liver, causing damage and, crucially, spilling into the bloodstream. This overflow results in cholestatic pruritus – intense, debilitating itching.
The itch associated with Alagille syndrome is particularly challenging for both patients and caregivers. As Jay Sandstrom, a caregiver whose son Finley has Alagille syndrome, described in a recent column, the itching isn’t always obvious to an outside observer. It can manifest as subtle scratching, rubbing against surfaces, or fidgeting. However, for those familiar with the condition, these behaviors are clear indicators of discomfort.
How Livmarli Works
Livmarli addresses the underlying cause of cholestatic pruritus by blocking the ileal bile acid transporter (IBAT), a protein responsible for reabsorbing bile acids from the intestines back into the liver. By inhibiting IBAT, Livmarli increases the amount of bile excreted in the stool, reducing the overall bile acid pool in the body. This, in turn, alleviates liver damage and reduces the intensity of the itching.
Long-Term Efficacy Demonstrated in MERGE Study
The long-term benefits of Livmarli were highlighted in data from the Phase 2 MERGE trial (NCT04168385). This trial evaluated the safety and efficacy of the drug in patients who had previously participated in Livmarli clinical trials. According to Dr. Doug Mogul, executive director of scientific affairs and engagement at Mirum, nearly all children who continued to receive Livmarli for seven years experienced ongoing improvements.
Specifically, the data showed clinically meaningful reductions in pruritus and serum bile acids, along with improvements in height. These findings suggest that the positive effects of Livmarli are not merely temporary but can be sustained over an extended period.
Beyond Itch Relief: Additional Benefits
While the reduction of itching is a primary goal of treatment for Alagille syndrome, Livmarli appears to offer broader benefits. Recent reports indicate the drug has even led to the clearing of severe skin growths in two boys with Alagille syndrome, demonstrating a potentially wider range of therapeutic effects.
data from the MARCH/MARCH-ON trials, also presented at the EASL congress, showed that Livmarli improved growth in patients with Progressive Familial Intrahepatic Cholestasis (PFIC), another liver disease where bile flow is impaired. This suggests that the medication may address growth challenges often associated with chronic liver conditions.
Managing the Itch: A Multifaceted Approach
While medication like Livmarli plays a crucial role in managing cholestatic pruritus, caregivers emphasize the importance of a comprehensive approach. Loose-fitting cotton clothing is often recommended to minimize skin irritation. Caregivers also learn to recognize subtle signs of itching and proactively address them.
As Finley Sandstrom’s father, Jay Sandstrom, notes, caregivers are “somewhat in control” of managing the condition. Medication provides a foundation, but a combination of strategies is often necessary to effectively alleviate the itch and improve a child’s quality of life.
Looking Ahead: Commercial Growth and Pipeline Momentum
Mirum Pharmaceuticals reported promising preliminary unaudited 2025 results in January 2026, demonstrating strong commercial growth and continued momentum in their pipeline. Livmarli is currently approved in the U.S. For the treatment of cholestatic pruritus in patients with Alagille syndrome three months of age and older. The ongoing research and positive clinical outcomes suggest a continued commitment to developing and improving treatments for this challenging condition.
The long-term data from the MERGE study and other trials provide encouraging evidence for the sustained benefits of Livmarli in managing Alagille syndrome. While the condition remains complex and requires a multifaceted approach to care, advancements in treatment options offer hope for improved outcomes and a better quality of life for affected children and their families.
