Maralixibat Side Effects and What Clinicians Should Know From EXPAND

Gastrointestinal adverse events were the most common safety finding with maralixibat (Livmarli) in the phase 3 EXPAND trial in ultra-rare cholestatic liver diseases.¹

In an interview with HCPLive, Jennifer Vittorio, MD, associate professor of pediatrics and medical director of pediatric liver transplantation at NYU Langone Health, discussed what clinicians should know about maralixibat’s safety profile, how to interpret the EXPAND results, and why screening for pruritus matters in all patients with cholestasis.

“My own clinical experience is that I find that these GI side effects are often transient in nature,” Vittorio said. “Usually they’re the most severe when you initiate the medication, and typically what I’ve observed is that they often resolve within the first few days of administration, or at least in the first week or so.”

Maralixibat Diarrhea and GI Adverse Events in EXPAND

Because maralixibat blocks ileal bile acid reabsorption and increases fecal bile acid excretion, most reported adverse events are gastrointestinal, Vittorio said. In EXPAND, diarrhea occurred in 64.0% of patients receiving maralixibat vs 11.1% receiving placebo, abdominal pain in 20.0% vs 14.8%, and increased alanine aminotransferase in 8.0% vs 3.7%.¹

Grade ≥3 adverse events occurred in 24.0% vs 22.2% of patients. None of the serious adverse events with maralixibat were considered treatment related, and no deaths occurred.¹ Vittorio said she counsels families before starting treatment on what to watch for, so symptoms can be triaged early.

Interpreting the One-Point ItchRO(Obs) Improvement

“While a one point improvement when you say that out loud may not seem like much, again we’re talking about a five point scale,” Vittorio said. “So a one point decrease, if you were to go from moderate or severe symptoms down to something that’s mild, or to have days where you’re completely symptom free, that’s hugely impactful and meaningful for patients and their caretakers.”

In EXPAND, maralixibat produced a placebo-adjusted improvement of 0.98 points on the 0 to 4 ItchRO(Obs) scale in pediatric patients (P = .0004). Among patients with biliary atresia and a native liver, pruritus improved on 96.4% of days vs 52.2% with placebo (P = .0045).¹

Access to IBAT Inhibitors Beyond Alagille Syndrome and PFIC

The US Food and Drug Administration (FDA) first approved maralixibat in September 2021 for cholestatic pruritus in Alagille syndrome, and the label now covers patients aged ≥3 months. Approval for progressive familial intrahepatic cholestasis (PFIC) followed in March 2024 and was expanded to patients aged ≥12 months in July 2024.¹,²

Vittorio said she has grown comfortable prescribing ileal bile acid transporter inhibitors but has been frustrated by difficulty gaining access to them for patients outside those indications who she believes would benefit. Mirum plans to submit a supplemental new drug application in the first half of 2027 based on EXPAND, which has not yet been peer reviewed.¹

Screening for Pruritus in Biliary Atresia

Vittorio said pruritus has historically received less attention in diseases such as biliary atresia than in Alagille syndrome and PFIC, creating a misconception that it is not a symptom to look for. She urged clinicians to screen all patients with cholestasis for signs of pruritus and to educate caregivers, pediatricians, and local providers who see these patients less often.

Editor’s Note: Disclosures for Jennifer Vittorio, MD, include Mirum Pharmaceuticals.

References

1. Mirum Pharmaceuticals announces primary endpoint met in phase 3 EXPAND study of Livmarli (maralixibat) in ultra-rare cholestatic liver diseases. News release. Mirum Pharmaceuticals. October 12, 2026. Accessed October 16, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-EXPAND-Study-of-LIVMARLI-maralixibat-in-Ultra-Rare-Cholestatic-Liver-Diseases/default.aspx

2. Livmarli (maralixibat). Prescribing information. Mirum Pharmaceuticals. Accessed October 16, 2026. https://files.mirumpharma.com/livmarli/livmarli-prescribinginformation.pdf