Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): A randomised phase 2 study
The Lancet Nov 04, 2021
Gonzales E, Hardikar W, Stormon M, et al. - Maralixibat (an apical, sodium-dependent, bile acid transport inhibitor) affords the first agent that confers durable and clinically meaningful improvements in cholestasis in children with Alagille syndrome. Maralixibat might serve as a new therapeutic paradigm for chronic cholestasis in Alagille syndrome.
This is a placebo-controlled, randomized withdrawal period (RWD), phase 2b study (ICONIC) with open-label extension in children (aged 1–18 years) with Alagille syndrome, who had more than three times the normal serum bile acid (sBA) levels and intractable pruritus.
Participants received maralixibat 380 μg/kg once per day for 18 weeks, thereafter were randomized (1:1) to continue maralixibat or receive placebo for 4 weeks.
Subsequently, all patients were administered open-label maralixibat until week 48, and doses were increased up to 380 μg/kg twice per day during the long-term extension (204 weeks reported).
The primary endpoint (mean sBA alteration during the RWD in patients with at least 50% sBA decrease by week 18) was met (least square mean difference –117 μmol/L).
Improvements in sBA (–96 μmol/L, –162 to –31) and pruritus (–1·6 pts, –2·1 to –1·1) were evident from baseline to week 48.
All improvements remained maintained in those who continued to week 204 (n=15).
Safety as well as good tolerability of maralixibat was generally observed throughout.
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