Article Text
Abstract
Patients with progressive familial intrahepatic cholestasis (PFIC) may have continued hepatic damage leading to liver transplantation (LT). Efficacy and safety of odevixibat, an ileal bile acid transporter inhibitor, were assessed in patients with PFIC in the phase 3 PEDFIC 1 and PEDFIC 2 studies. In a pooled analysis of data from these studies, we analysed native liver survival (NLS) in odevixibat-treated patients who met serum bile acid (sBA) treatment response criteria (sBAs reduced ≥70% or levels ≤70 µmol/L at 6 months). NLS was also analysed in partial sBA responders (patients with sBA reductions ≥30% to <70% at 6 months) and nonresponders (patients with sBA reductions <30% at 6 months or who underwent LT or discontinued treatment before 6 months).
PEDFIC 1 was a 24-week, randomised, placebo-controlled study in children with PFIC1 or PFIC2. PEDFIC 2 is an ongoing 72-week extension study in patients of any age with any PFIC type. This pooled analysis spans from patients’ first dose of odevixibat to a cut-off date of 31 January 2022.
Of 98 patients analysed (mean treatment duration, 88 weeks), 35 (36%) were sBA responders, 14 (14%) were partial sBA responders, and 49 (50%) were nonresponders. Mean sBA reductions at 6 months were 87% in responders and 44% in partial responders; there was a mean increase of 27% in nonresponders. All 35 sBA responders and 13 of the 14 partial sBA responders remained transplant free; 8 of the 49 nonresponders underwent LT (figure 1). sBA responders had mean improvements at week 24 of treatment vs baseline in alanine aminotransferase and total bilirubin levels.
sBA decreases at 6 months were strongly associated with NLS for up to 3 years in odevixibat-treated patients with PFIC.
Disclosures R.J. Thompson: Albireo and Mirum – Consultant; Generation Bio – Consultant and stock options; Rectify Therapeutics – Consultant and stockholder
C. Clemson, V. Valcheva, Q. Ni, Q. Yu, and J.P. Mattsson: Albireo – Employment
E. Sturm: Albireo and Mirum – Consultant and research support; Univar – Consultant; Orphalan – Speaker’s fee
H.J. Verkade: Ausnutria BV, Albireo, Danone/Nutricia Research, Intercept, Mirum, Orphalan, and Vivet – Consultant
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.