Children with progressive familial intrahepatic cholestasis (PFIC) who received odevixibat in the 24-week PEDFIC 1 study had significant reductions in total serum bile acids (sBAs) vs placebo-treated patients. Odevixibat was approved in 2021 in the European Union for treatment of PFIC in patients ≥6 months old. Here, we evaluated the effect of concomitant ursodeoxycholic acid (UDCA) on sBA concentrations in odevixibat-treated patients from PEDFIC 1 (n=42) who met sBA response (R) criteria or not; we also assessed whether excluding UDCA concentrations from total sBAs altered the proportion of patients with sBA R.

Patients eligible for PEDFIC 1 had elevated sBAs at screening. Concomitant UDCA was allowed provided the patient’s dose was stable. The threshold for sBA R was sBAs ≤70 μmol/L or sBAs reduced ≥70% from baseline (BL). The PEDFIC 1 per-protocol definition of sBA R was based on average measurements taken at weeks 22 and 24; those not meeting this criteria, including early-exit patients, were considered nonresponders (NRs). Using this per-protocol definition, rates of sBA R excluding the contribution of UDCA were also analysed. Finally, the proportion of patients who met sBA R was re-evaluated to include the last available sBA assessment for early-exit patients. sBA concentration and composition (ie, total, primary, and secondary sBAs, including UDCA) were evaluated at BL and at the end of treatment (EOT). Secondary sBA concentrations (and therefore, total sBAs) were evaluated with and without UDCA concentration included.

In the primary analysis of PEDFIC 1 study data, 14/42 patients met criteria for sBA R at EOT. When using the same per-protocol definition but excluding UDCA concentrations, 13/42 of patients met sBA R criteria. Using an updated R definition, 17/42 patients had an sBA R (3 early-exit patients were now counted as having an sBA R). Median concentrations of total and primary sBAs decreased considerably from BL to EOT in these Rs both with and without UDCA; these parameters remained largely unchanged in NRs regardless of whether UDCA concentration was considered (table 1). In all odevixibat-treated patients regardless of sBA R status, median values for secondary sBAs without UDCA at BL and at EOT were near 0 (table 1).

The proportion of patients with sBA R to odevixibat in PEDFIC 1 did not change appreciably when serum UDCA concentrations were excluded from total sBA levels. In patients with sBA R per an updated definition, large reductions in sBAs occurred whether or not UDCA concentration was included.