Alagille Syndrome
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Maralixibat shows clinically meaningful improvements in cholestasis in ALGS

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Children with Alagille syndrome (ALGS) treated with Maralixibat experience durable and clinically meaningful improvements in cholestasis, according to a study.

In the randomized withdrawal period of the phase 2b ICONIC study, 29 children with ALGS who had elevated serum bile acid (sBA) levels and intractable pruritus received maralixibat 380 μg/kg once per day for 18 weeks before being randomly assigned to continue maralixibat or receive placebo for 4 weeks. After the 4 weeks, all patients received open-label maralixibat until week 48. During a long-term extension period, doses were increased up to 380 μg/kg twice per day.

Patients switched to placebo after 18 weeks had significant increases in sBA and pruritus. Patients who remained on maralixibat maintained treatment effect.

This study met its primary endpoint of mean sBA change during the randomized withdrawal period in participants with ≥ 50% sBA reduction by week 18. At week 48, sBA and pruritus had improved from baseline.

All of the 15 participants who continued treatment till week 204 maintained improvements.

Gastrointestinal related adverse events were the most frequently reported although most were mild-to-moderate in severity.

Gonzales E, Hardikar W, Stormon M, et al. Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study. Lancet. 2021; DOI:https://doi.org/10.1016/S0140-6736(21)01256-3