Effects of odevixibat on pruritus and bile acids in children with cholestatic liver disease: Phase 2 study

•Odevixibat is a potent, selective, oral IBAT inhibitor.•This phase 2 study evaluated odevixibat in pediatric patients with cholestasis.•Odevixibat was well tolerated, reduced bile acids, and improved pruritus and sleep.•Odevixibat has potential to advance treatment of cholestatic diseases. Ileal bile acid transporter inhibition is a novel therapeutic concept for cholestatic pruritus and cholestatic liver disease progression. Odevixibat, a potent, selective, reversible ileal bile acid transporter inhibitor, decreases enteric bile acid reuptake with minimal systemic exposure. Oral odevixibat safety, tolerability, and efficacy in pediatric patients with cholestatic liver disease and pruritus were evaluated. In this phase 2, open-label, multicenter study, children received 10‒200 μg/kg oral odevixibat daily for 4 weeks. Changes in serum bile acid levels (primary efficacy endpoint), pruritus, and sleep disturbance were explored. Twenty patients were enrolled (8 females; 1‒17 years; 4 re-entered at a different dose). Diagnoses included progressive familial intrahepatic cholestasis (n = 13; 3 re-entries), Alagille syndrome (n = 6), biliary atresia (n = 3), and other intrahepatic cholestasis causes (n = 2; 1 re-entry). Mean baseline serum bile acid levels were high (235 µmol/L; range, 26‒564) and were reduced in the majority (−123.1 μmol/L; range, −394 to 14.5, reflecting reductions of up to 98%). Patient-reported diary data documented improved pruritus (3 scales) and sleep. With 100 μg/kg, mean (SEM) decrease was 2.8 (1.1) points for pruritus (visual analogue itch scale 0−10) and 2.9 (0.9) points for sleep disturbance (Patient-Oriented Scoring Atopic Dermatitis scale 0−10). Reduced pruritus correlated significantly with reduced serum bile acids (P ≤ 0.007). Significant correlations were also observed between autotaxin levels and pruritus. All patients completed the study. No serious adverse events were treatment related; most adverse events, including increased transaminases, were transient. Orally administered odevixibat was well tolerated, reduced serum bile acids, and improved pruritus and sleep disturbance in children with cholestatic diseases.