O12 Hepatic parameters, growth, and sleep with responders and nonresponders to odevixibat treatment: pooled data from the PEDFIC 1 and PEDFIC 2 studies in children with progressive familial intrahepatic cholestasis

Introduction/Background Progressive familial intrahepatic cholestasis (PFIC) is a group of inherited paediatric cholestatic liver diseases. In the phase 3 PEDFIC 1 and PEDFIC 2 studies, odevixibat, an ileal bile acid transporter inhibitor, reduced serum bile acids (sBAs) and improved pruritus in patients with PFIC. Aim Using pooled data from PEDFIC 1 and PEDFIC 2, we analysed hepatic biochemical parameters, growth, and sleep changes in patients who responded to odevixibat (Rs) versus nonresponders (NRs) after up to 72 weeks of treatment. Subjects and Methods PEDFIC 1 was a 24-week, randomised, placebo-controlled study in children with PFIC1 or PFIC2. PEDFIC 2 is an ongoing 72 week, open-label extension study in patients with any type of PFIC. This pooled analysis spans from patients’ first dose of odevixibat to a cut-off date of 4 December 2020. Treatment Rs met either sBA response criteria (defined per the PEDFIC 1 study protocol) or sBA and/or pruritus response criteria (table 1). Assessments included change from baseline in transaminases, total bilirubin, growth, and sleep parameters. Results In total, 84 patients (mean age, 5.0 years) received odevixibat (median [range] exposure, 53 [3−128] weeks). Overall, 30/81 (37%) patients were sBA Rs and 49/84 (58%) were sBA and/or pruritus Rs during weeks 0−72. From baseline to week 72, Rs had mean improvements in transaminases and total bilirubin levels (table 1). Patients who were NRs had more pronounced growth deficits at baseline; however, with treatment, mean height and weight Z scores increased in both Rs and NRs (table 1). Rs and NRs had similar sleep characteristics at baseline. After 72 weeks of treatment, sBA Rs had large decreases in caregiver-reported percentage of days patients had scratching associated with bleeding, needed soothing, and needed help falling asleep (–47%, –76%, –75%, respectively); increases or smaller changes were observed in sBA NRs (3%, –24%, −35%, respectively). Comparable results were observed in sBA and/or pruritus Rs. Drug-related treatment-emergent adverse events (TEAEs) were reported in 47% and 39% of sBA Rs and NRs, respectively, and in 49% and 31% of sBA and/or pruritus Rs and NRs; no drug-related serious TEAEs were reported. Summary and Conclusion Odevixibat treatment for up to 72 weeks in patients with PFIC was associated with improvement in hepatic health, quality of sleep, and growth, with greater improvement observed in Rs compared with NRs. Odevixibat was generally well tolerated in Rs and NRs. Conflict of Interest Declaration P. McKiernan: Sobi AB, Albireo – Consultant E. Sturm: Albireo, Mirum, and Astellas – Consultant and/or received travel support B.M. Kamath: Albireo, Mirum, and Audentes – Consultant; Albireo and Mirum – Unrestricted educational grant R.J. Thompson: Albireo, Alnylam, Evox Therapeutics, Generation Bio, Mirum Pharma, Rectify Therapeutics, Retrophin, Qing Therapeutics, and Sana Biotechnology – Consultant E. Gonzalès: Laboratoires CTRS, Mirum, and Albireo – Consultant A. Lachaux: GMP-Orphan, CSL Behring – Consultant U. Baumann: Albireo, Mirum, Alnylam, Vivet, and Nestlé – Consultant T. Grammatikopoulos: Albireo – Consultant S.J. Karpen: Albireo, Intercept, LogicBio, and Mirum– Consultant E. Shteyer, P. Czubkowski, R. Artan, B. Dalgic, H. Özen, and G. Gupte: Nothing to disclose Q. Ni, L. Kjems, P. Horn: Albireo – Current or former employment This study was sponsored by Albireo. Medical writing and editorial assistance were provided by Peloton Advantage, LLC, an OPEN Health company, and were funded by Albireo Pharma, Inc.

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