Rare liver itch pill eased itching and cut bile acids by 69%

Maralixibat (Livmarli), an oral drug already used for itch in two rare liver conditions, cut cholestatic itch and lowered blood bile acids in people with other ultra-rare cholestatic liver diseases in the phase 3 EXPAND trial. In children, the main analysis group, average worst daily itch fell by 1.81 points on a 0 to 4 scale against 0.83 on placebo, a 0.98-point gap (p=0.0004). Across everyone treated, serum bile acids fell 70.1% from baseline on maralixibat against 3.5% on placebo, a 69.0% treatment effect (p<0.0001).

Mirum Pharmaceuticals announced the topline results on 12 October 2026 and hosted an investor call the same morning. The company plans a US supplemental application in the first half of 2027. The figures have not yet appeared in a peer-reviewed journal or at a major liver meeting.

About half of those enrolled had biliary atresia with their own liver still in place, a group with no approved drugs for cholestatic itch. In that subgroup the itch and bile-acid benefits were at least as large as in the wider trial.

What cholestatic itch is

Cholestasis means bile flow out of the liver is reduced or blocked. Bile acids then build up in blood and tissues. Many people with cholestasis develop intense itch (pruritus) that can dominate daily life, disturb sleep and, in children, disrupt feeding and growth. Scratching can break the skin. Standard itch medicines, including antihistamines, often help little because the driver is cholestasis, not histamine.

Biliary atresia is a rare condition of infancy in which bile ducts outside and inside the liver are inflamed and scarred. Surgeons often create a drainage path (a Kasai portoenterostomy) soon after diagnosis. Even after that operation, many children keep a native liver for years but still live with cholestasis and severe itch. Biliary atresia is the leading reason for liver transplants in children, a point underlined in a 2022 review in the Journal of Clinical Medicine.

Maralixibat is already approved in the US for cholestatic pruritus in Alagille syndrome (from age 3 months) and progressive familial intrahepatic cholestasis (PFIC, from age 12 months). EXPAND tested whether the same drug helps people with other rare cholestatic diseases that sit outside those labels, including biliary atresia.

How maralixibat works

Maralixibat blocks the ileal bile acid transporter (IBAT) in the small intestine. That transporter normally reabsorbs bile acids so they can cycle back to the liver. Blocking it lets more bile acids leave the body in stool, which lowers circulating levels. Lower bile acids are thought to ease cholestatic itch, though itch biology is complex and not fully mapped. The same mechanism sits behind odevixibat (Bylvay), another IBAT inhibitor used in some cholestatic diseases.

A chemical diagram of maralixibat appears as the hero image for this article (public-domain structure drawing on Wikimedia Commons).

Who was in EXPAND

EXPAND (NCT06553768) is a randomised, double-blind, placebo-controlled phase 3 study. Sites span North America, Europe, the Middle East and South America. Mirum's topline release says 52 people took part in the reported double-blind analysis: 46 children and 6 adults. They were assigned to maralixibat oral solution 285 µg/kg twice daily or matching placebo for 20 weeks. (The public trial record lists a target dose near 300 µg/kg twice daily after a short escalation; the company reported the 285 µg/kg figure with the results.)

Eligible people were aged 6 months and older with a rare cholestatic liver disease plus persistent cholestatic itch that had not responded well to other options. Diagnoses already covered by maralixibat's US label (Alagille syndrome and PFIC) were excluded, as were primary biliary cholangitis and primary sclerosing cholangitis. The protocol also required raised serum bile acids and a minimum average itch score during screening. Roughly half of those enrolled had biliary atresia with a native liver. Other rare diagnoses listed as examples on ClinicalTrials.gov include alpha-1 antitrypsin deficiency, ARC syndrome, Caroli disease and several metabolic cholestatic disorders.

The main endpoint in children was the change from baseline in average worst daily ItchRO(Obs) severity score during weeks 13 to 20. ItchRO(Obs) is a caregiver-reported scale from 0 (no itch) to 4 (very severe itch). Secondary measures included the share of days with itch improvement and the relative change in total serum bile acids. The same itch and bile-acid measures were pre-specified in the biliary atresia subgroup.

Our guide to open-label versus blinded trials explains why a double-blind design matters for a symptom endpoint like itch.

The main results

Mirum reported that EXPAND met its primary endpoint and all five pre-specified secondary endpoints. Coverage in HCPLive and Fierce Pharma matches the company figures below.

Itch in children (primary)

In context, mean baseline itch was about 2.65 on the 0 to 4 scale in the company's investor discussion of the data. A drop of nearly two points on the active arm is a large move on that scale. Placebo also improved, which is common in itch trials, so the 0.98-point gap is the figure that matters for judging the drug.

Children on maralixibat had itch improvement on 86.0% of days against 49.1% on placebo (difference 36.9 percentage points, p=0.0008). Improvement meant a worst daily score of 1 or less, or a fall of at least 1 point from baseline.

Serum bile acids

Across the full double-blind population (25 on maralixibat, 27 on placebo), serum bile acids fell 70.1% from baseline on maralixibat and 3.5% on placebo. The treatment effect versus placebo was 69.0% (p<0.0001). That fall fits the drug's mechanism and supports the idea that itch relief tracked a biological change, diary scores alone.

Biliary atresia with native liver

Those numbers matter because earlier IBAT inhibitor trials aimed at changing the course of biliary atresia itself did not succeed. Mirum's earlier phase 2 study of maralixibat given after Kasai surgery missed its bilirubin goal. In July 2026 Ipsen said the phase 3 BOLD trial of odevixibat (Bylvay) in infants with biliary atresia did not improve native-liver survival versus placebo. EXPAND asked a different question: does maralixibat ease itch and lower bile acids in people who already have cholestatic disease, including biliary atresia survivors with their own liver? On that narrower goal, the topline answer was yes.

Jennifer Vittorio of NYU Langone Health, quoted in Mirum's release, called the size and consistency of the itch and bile-acid changes compelling, including for biliary atresia. Patient advocate Jen Lau of Biliary Atresia Research and Education (BARE) said families living with these diseases have few treatment options today.

Side effects

Treatment-emergent adverse events were reported in 96.0% on maralixibat and 96.3% on placebo. Grade 3 or higher events affected 24.0% and 22.2%. Serious events affected 20.0% and 18.5%. Mirum said none of the serious events on maralixibat were judged related to the drug. One person on maralixibat left the study because of an adverse event. No deaths were reported in the double-blind period.

Diarrhoea was the standout difference, as expected for an IBAT blocker:

Mirum said no one stopped because of diarrhoea, and that the safety pattern matched earlier maralixibat studies. Families and clinicians will still want the full tables, including how long diarrhoea lasted, whether doses were held, and whether nutrition or growth were affected in younger children. Fat-soluble vitamin levels and growth charts are especially relevant when children already have cholestatic liver disease.

What is already approved, and what comes next

In the US, Livmarli oral solution is approved for cholestatic pruritus in Alagille syndrome and PFIC. A tablet form followed later. EXPAND is meant to support a broader label covering other ultra-rare cholestatic diseases with refractory itch, with biliary atresia a large part of that unmet need. That would be a third US itch indication for the same molecule.

Mirum plans to file a supplemental New Drug Application with the FDA in the first half of 2027. Approval would expand an existing Livmarli label, not create a brand-new first approval for the molecule. Europe and UK filing timing was not set out in the topline release. For how regulators weigh trial evidence, see our guide to how new medicines get approved.

Limitations to keep in mind

• Topline company data. Peer-reviewed full results, with confidence intervals and baseline tables, are still to come.
• Small numbers. Fifty-two people in total, and 25 in the biliary atresia native-liver subgroup, limits precision and subgroup claims.
• Symptom endpoint. Itch scores rely on caregivers and patients. Blinding helps, but diarrhoea rates were much higher on active drug, which can unblind some participants.
• Twenty weeks. Longer open-label follow-up in EXPAND should show whether itch control and tolerability hold.
• Disease course untouched. EXPAND did not claim to delay transplant or change native-liver survival. Earlier disease-modification trials of IBAT inhibitors in biliary atresia failed. Families should separate itch relief from hopes about transplant timing.
• Label exclusions in the trial. People with Alagille syndrome or PFIC were kept out because they already have access pathways for maralixibat; EXPAND was about everyone else with rare cholestatic itch.
• Dose wording. The company reported 285 µg/kg twice daily; ClinicalTrials.gov describes a protocol target near 300 µg/kg twice daily after escalation. Full publications should clarify the analysed dose.

How this fits other rare-disease news

EXPAND adds a positive phase 3 signal in a rare-disease space that often struggles with small samples and hard endpoints. It sits alongside other recent rare-disease readouts on this site, such as bitopertin in erythropoietic protoporphyria and atacicept's two-year IgA nephropathy data. For readers tracking what happens when a trial misses, our note on what a failed trial can still tell you is a useful companion to those earlier biliary atresia disease-course trials, including Ipsen's BOLD study.

People with cholestatic itch linked to a rare liver disease can ask their hepatology team whether an IBAT inhibitor trial or expanded-access route is open locally, and can follow patient groups such as Biliary Atresia Research and Education (BARE) for updates as Mirum prepares its filing.

This article explains published research and company announcements. It is not medical advice. Talk to your own doctor or specialist team before changing any treatment.