Maralixibat treatment leads to marked improvements in pruritus and quality of life in patients with Alagille syndrome (ALGS), according to a study published in Hepatology Communications

The finding is based on results from 2 randomized placebo-controlled clinical trials investigating the effect of maralixibat in 57 children with severe cholestasis secondary to ALGS.

Maralixibat, marketed under the brand name Livmarli, is an apical sodium-dependent bile acid transporter (ASBT) inhibitor. ASBT normally controls the enterohepatic circulation of bile acids so inhibiting the function of the protein leads to more bile acids being excreted in the feces, thereby reducing the levels of systemic bile acids.


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The results of the trials showed that maralixibat leads to statistically and clinically significant improvements in pruritus and quality of life as well as in multidimensional fatigue at week 48. Moreover, serum bile levels of bile acids and cholesterol as well as the platelet count decreased in the blood of patients treated with maralixibat.

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On the contrary, levels of alanine aminotransferase increased. The levels of total bilirubin and albumin stayed the same. The observed changes were durable at week 72 and at the end of the treatment period.

There were no deaths during the trial but 2 patients underwent liver transplantation. Treatment had to be discontinued in 9 patients due to treatment-emergent adverse events. Of these 6 were increased alanine aminotransferase and total bilirubin. 

The researchers concluded that the “interpretation of these findings is complicated” because of the complex natural history of severe cholestasis in patients with ALGS.

ALGS is characterized by bile duct paucity mainly due to a mutation in the JAG1 gene, disrupting the Notch signaling pathway. This causes the buildup of bile in the liver leading to hepatic damage. Symptoms include pruritus, jaundice, and cholestasis.

Reference

Shneider BL, Spino CA, Kamath BM, et al. Impact of long-term administration of maralixibat on children with cholestasis secondary to Alagille syndrome. Hepatol Commun. Published online June 7, 2022. doi:10.1002/hep4.1992.