EFFICACY AND SAFETY OF ODEVIXIBAT OVER 48 WEEKS: POOLED DATA FROM THE PHASE 3 ASSERT AND ASSERT-EXT STUDIES IN PATIENTS WITH ALAGILLE SYNDROME

ABSTRACT: Objectives and Study: Cholestasis in Alagille syndrome (ALGS) is associated with bile acid (BA) accumulation in the liver with spill-over into the systemic circulation, as well as severe pruritus that can impair sleep. Here, we describe outcomes with odevixibat, an ileal BA transporter inhibitor, using pooled data from the phase 3 ASSERT and ASSERT-EXT trials in patients with ALGS. Methods: In ASSERT (NCT04674761), patients with ALGS with history of significant pruritus and elevated serum BAs (sBAs) were randomised 2:1 to odevixibat 120 µg/kg/day or placebo, respectively, for 24 weeks. Patients who completed ASSERT could enter ASSERT-EXT (NCT05035030), an ongoing, 72-week extension study where all patients received odevixibat 120 µg/kg/day. Here, data from odevixibat-treated patients in ASSERT and/or ASSERT-EXT were pooled (from first odevixibat dose to a data cut-off of 17 July 2023). Observer-reported scratching scores, sleep parameters, and sBA levels were assessed through 48 weeks of treatment. Results: At the data cut-off, the pooled population comprised 52 odevixibat-treated patients (mean age, 6.5 years; 48% female; median [range] odevixibat exposure, 73 [16–110] weeks). Odevixibat treatment for up to 48 weeks resulted in rapid and significant mean improvements in pruritus and reductions in sBA levels vs baseline (Figure). There were also significant decreases from baseline to weeks 45−48 in multiple sleep parameters, including tiredness and mean percentage of days patients needed help falling asleep, needed soothing, and slept with their caregiver (Figure). Treatment-emergent adverse events (TEAEs) were reported in 49 of 52 (94%) odevixibat-treated patients. The most common TEAE was diarrhoea (n=18/52 [35%]). At the data cut-off, 1 patient had a TEAE (blood bilirubin increased) that led to study discontinuation. Conclusions: In patients with ALGS, odevixibat treatment for up to 48 weeks led to significant improvements in pruritus and sleep and significant reductions in sBA levels. TEAEs in this pooled analysis were consistent with previously reported results