Two attending physicians commented in The Lancet on the new findings of the phase 2 placebo-controlled, randomized withdrawal period, open-label, extension ICONIC study for Alagille syndrome (ALGS).

Maralixibat (Livmarli™), developed by Mirum Pharmaceuticals, is used for patients with cholestatic liver diseases such as ALGS. Alyssa Kriegermeier, MD, and Sarah A. Taylor, MD, from the Ann & Robert H. Lurie Children’s Hospital of Chicago in Illinois studied 4-year data demonstrating the safety and efficacy of maralixibat. The study findings were recently published in The Lancet.

“Two earlier phase 2 trials have evaluated maralixibat in pediatric patients with [ALGS], the ITCH (NCT02057692) and IMAGO (NCT01903460) studies, with long-term extensions of the IMAGO trial ongoing (IMAGINE-1 NCT02047318 and IMAGINE-II NCT02117713),” Drs. Kriegermeier and Taylor said.

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“Neither trial met the primary endpoint; however, maralixibat was generally well tolerated, and reduced pruritus was noted.”

Data Published From Pivotal Study on Alagille Syndrome Treatment Maralixibat

In the ICONIC study, patients showed a significant reduction in serum bile acids (sBA) from baseline. This reduction was only maintained during the withdrawal period by patients receiving maralixibat.

Hence, the ICONIC study was the first study of maralixibat for pediatric patients with ALGS to meet the primary endpoint (ie, the mean change in sBA during the randomized withdrawal period between maralixibat and placebo groups and in participants who had previously achieved a reduction in sBA from baseline by 50%).

Treatment with maralixibat also reduced pruritus and improved quality of life and fatigue scores from baseline to week 48.

Maralixibat Improved Event-Free Survival Rates for Patients With Alagille Syndrome

“Future studies that can assess for changes in transplant-free survival in patients with ALGS treated with maralixibat, and additional ongoing studies of maralixibat (and other [apical sodium-dependent bile acid transporter] inhibitors) assessing for long-term effects on patient symptoms, weight gain or growth, and disease trajectory are expected to further inform management of ALGS,” they concluded.


Kriegermeier A, Taylor S. Apical sodium-dependent bile acid transporter inhibition in children with Alagille syndrome. Lancet. 2021;398(10311):1544-1545. doi:10.1016/S0140-6736(21)01447-1