The  U.S. Food and Drug Administration (FDA) has approved odevixibat (Bylvay) to treat cholestatic pruritus in patients from 12 months of age with Alagille syndrome. In 2021, the FDA approved maralixibat (Livmarli) to treat cholestatic pruritus in patients from 12 months of age with Alagille syndrome. In March 2023, the Livmarli label was expanded and is FDA approved for the treatment of cholestatic pruritus in people with Alagille syndrome three months and older. Odevixibat is an ileal bile acid transport inhibitor while maralixibat is an apical sodium dependent bile acid transporter inhibitor.

Alagille syndrome is a rare, genetic, multisystemic disorder. Approximately 95% of children with this condition present with chronic cholestasis and up to 88% present with severe, intractable pruritus.

 The approval  of odevixibat is largely based on the data from the Phase III ASSERT study, a double-blind, randomized, placebo-controlled trial that assessed the safety and efficacy of 120 µg /kg/day odevixibat for 24 weeks in patients aged 0 to 17 years of age with a genetically confirmed diagnosis of Alagille syndrome. The study met the primary endpoint showing statistically significant improvement in pruritus as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale) compared to placebo. More than 90% of patients given odevixibat were pruritus responders (≥ 1 point change at any time during 24 weeks).

In the study, there were no patient discontinuations and 96% of patients rolled over into the open-label extension study. Odevixibat adverse event profile was similar to the placebo group with the exception of a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo).

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