First results on maralixibat for rare cholestatic itch due by year’s end
Global trial testing oral therapy in rare liver diseases now fully enrolled
Written by |
A global clinical trial testing Mirum Pharmaceuticals’ oral therapy maralixibat in people with itching, or pruritus, due to rare cholestatic conditions has finished enrollment, and top-line results are expected before year’s end.
Mirum announced these updates in a company press release, which noted that the trial’s primary goal is “change in pruritus severity” over 20 weeks, or about five months.
Maralixibat is already approved in the U.S. and other countries under the name Livmarli for the treatment of itching associated with Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), two rare genetic disorders that cause cholestasis, or slowed flow of the digestive fluid bile.
This Phase 3 trial, dubbed EXPAND (NCT06553768), is testing the therapy for other rare cholestatic diseases. It was estimated to enroll 90 participants, ages 6 and older, across a dozen countries worldwide.
“Completing enrollment in EXPAND marks an important milestone in our efforts to broaden the reach of LIVMARLI to additional patients living with cholestatic pruritus,” said Joanne Quan, MD, Mirum’s chief medical officer. “Itch due to cholestasis profoundly affects the daily lives of patients and their families.”
Normally, bile is made in the liver and shipped to the intestines through a series of tubes called bile ducts. When this flow is blocked or stalled, bile builds up to toxic levels in the liver and leaks into the bloodstream, which can lead to liver damage and cholestasis symptoms such as itching.
“For the patients and families living with rare liver diseases, cholestatic pruritus isn’t just an itch — it can be relentless, exhausting, and life-altering,” said Mercedes Martinez, MD, a professor at Columbia University Vagelos College of Physicians and Surgeons. “Yet for many of these conditions, there are still no approved treatment options for pruritus.”
That’s the case for biliary atresia, a rare disorder affecting infants in which the bile ducts are absent or blocked from birth.
Global EXPAND study testing maralixibat for treating itching
Mirum hopes maralixibat can fill a treatment void for these children.
Quan said: “We aim to address the unmet medical needs of these patients by leveraging our established IBAT mechanism.”
Maralixibat is designed to suppress the ileal bile acid transporter (IBAT), a protein that normally helps recycle bile acids — bile’s main components — in the intestines back to the liver. Thus, the medication is expected to increase bile excretion in feces, relieving the buildup in the liver and bloodstream and easing itching.
After demonstrating that maralixibat is safe and effective at reducing itch in people with Alagille and PFIC, Mirum launched EXPAND to evaluate whether the therapy can also benefit individuals with other rare cholestatic diseases, specifically patients whose condition has failed to respond to other therapies and who have no other treatment options.
“The EXPAND study marks an important milestone in exploring whether a targeted therapy like LIVMARLI can offer meaningful relief to patients who urgently need better treatment options,” Martinez said.
Trial participants, including those with biliary atresia, are being randomly assigned to take either maralixibat (285 micrograms per kg) or a placebo, twice daily, over a period of about five months.
The main goal is to assess whether the therapy eases itch severity, as measured with the caregiver-reported ItchRO(Obs) severity score. Secondary goals include changes in blood bile acid levels and other markers of cholestasis.
Families affected by biliary atresia and other rare cholestatic conditions understand the relentless burden of itch. … The completion of enrollment in EXPAND brings hope that more patients may soon have access to a much-needed treatment option.
After the initial placebo-controlled portion of the study, all participants will be treated with maralixibat and monitored for efficacy and safety outcomes.
“Families affected by biliary atresia and other rare cholestatic conditions understand the relentless burden of itch,” said Jen Lau, co-founder and executive director of BARE (Biliary Atresia Research and Education). “The completion of enrollment in EXPAND brings hope that more patients may soon have access to a much-needed treatment option.”
