Phase 3 Trial Evaluating Maralixibat for Cholestasis-Related Pruritus
核心洞察
A Phase 3 clinical trial (EXPAND) is underway to assess maralixibat's efficacy in treating pruritus (搜索) associated with rare cholestatic conditions, excluding Alagille syndrome (搜索) and PFIC.
The EXPAND trial aims to enroll 90 participants aged 6 months and older across multiple sites in the U.S., South America, Europe, and the Middle East, with enrollment expected to conclude in 2026.
Participants will receive either maralixibat or a placebo, with the primary goal of assessing changes in the caregiver-reported ItchRO(Obs) severity score.
Mirum Pharmaceuticals is currently enrolling participants in a Phase 3 clinical trial, named EXPAND (NCT06553768), to evaluate the effectiveness of maralixibat in treating persistent itching, or pruritus (搜索), linked to rare cholestatic conditions. The study is designed for individuals who have not responded adequately to other treatments.
The EXPAND trial plans to enroll up to 90 individuals, aged 6 months and older, across various locations in the U.S., South America, Europe, and the Middle East. According to a press release from Mirum, recruitment is actively taking place at sites in Los Angeles, New Orleans, and New York, with the anticipation of completing enrollment by 2026.
Maralixibat's Current Approvals and Mechanism
Maralixibat, marketed as Livmarli in the U.S. and European Union, is already approved for treating pruritus (搜索) associated with Alagille syndrome (搜索) and progressive familial intrahepatic cholestasis (搜索) (PFIC). These rare genetic disorders are characterized by cholestasis (搜索), a condition where the flow of bile from the liver to the intestines is impaired.
Reduced bile flow can cause bile to accumulate in the liver and leak into the bloodstream, leading to symptoms such as pruritus (搜索). Untreated, excessive bile in the liver can result in irreversible liver scarring (搜索) (cirrhosis (搜索)) and liver failure, potentially requiring a liver transplant.
Trial Exclusions and Cholestasis Causes
The EXPAND trial will exclude individuals with Alagille, PFIC, intrahepatic cholestasis of pregnancy (搜索) (ICP), primary biliary cholangitis (搜索) (PBC), and primary sclerosing cholangitis (搜索) (PSC) who have not undergone a liver transplant. The trial also excludes patients with decompensated cirrhosis (搜索), complications of cirrhosis, and liver or bile duct cancers.
Cholestasis (搜索) can arise from various factors, including hepatitis, alcohol-associated liver disease, bacterial infections, gallstones, or inflammation of the pancreas. Gallstones, which are hard deposits of bile compounds, can obstruct bile ducts.
EXPAND Trial Design and Objectives
The EXPAND trial aims to determine if maralixibat can safely and effectively alleviate pruritus (搜索) in children and adults with rare cholestatic diseases who have not responded to other therapies. Participants must maintain a stable regimen of UDCA or anti-pruritus medications for 30 days before and throughout the study.
Participants will be randomly assigned to receive either 300 micrograms of maralixibat per kilogram of body weight (mcg/kg) or a placebo, administered orally once daily for a week, followed by twice daily for 19 weeks. Those initially assigned to maralixibat will continue receiving 300 mcg/kg twice daily for up to 39 weeks, while those on placebo will switch to 300 mcg/kg once daily for a week, then twice daily for 19 weeks.
The primary endpoint of the study is the change in the caregiver-reported ItchRO(Obs) severity score from baseline to the last two months of treatment. Scores range from 0 (no itching) to 4 (extreme itching). Changes in total blood levels of bile acids will also be assessed.
Mirum's Broader Pipeline
Mirum is also evaluating volixibat, another oral candidate, for its potential to reduce itching in PSC and PBC. Enrollment in the Phase 2b VISTAS trial (NCT04663308), testing volixibat in PSC patients, is expected to be completed in the second half of this year, with top-line data due in 2026. The ongoing Phase 2 VANTAGE trial (NCT05050136), evaluating volixibat in PBC patients, is expected to complete enrollment in 2026.
According to Chris Peetz, CEO of Mirum, 2024 was a significant year for the company, marked by continued leadership in cholestatic disease with a label expansion for Livmarli and positive interim analyses for volixibat in PSC and PBC.