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.