Introduction: In the 24-week PEDFIC 1 study (NCT03566238), odevixibat significantly reduced serum bile acids and improved pruritus in patients with progressive familial intrahepatic cholestasis (PFIC). To better understand odevixibat’s impact on liver function, we analyzed data on hepatic biochemical parameters and liver events from PEDFIC 1.

Method: Eligible children received placebo or odevixibat. Assessments included hepatic biochemical parameters (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin [TB]), liver-related treatment-emergent adverse events (TEAEs), and elevations in hepatic parameters evaluated using the modified evaluation for drug-induced severe hepatotoxicity (eDISH) approach. A Data Safety Monitoring Board (DSMB) reviewed prespecified hepatic events.

Results: In PEDFIC 1, 62 patients were randomized (n=20, placebo; n=42, odevixibat). Mean changes in ALT, AST, and TB levels are presented (Figure). Overall, 4/20 (20%) patients receiving placebo and 11/42 (26%) receiving odevixibat had liver-related TEAEs; the most common with odevixibat were ALT increased (n=6 [14%]; placebo, n=1 [5%]) and blood bilirubin increased (n=5 [12%]; placebo, n=2 [5%]). Potentially clinically significant ALT or AST elevations (ie, >3× baseline levels) were observed in 4 odevixibat-treated patients, but no concurrent TB elevations were observed. There were no confirmed cases of drug-induced liver injury (DILI); liver-related events were assessed as related to patients’ underlying disease or other causes. No patients developed liver decompensation.

Conclusion: Following odevixibat treatment in patients with PFIC, mean transaminase and TB levels decreased, whereas only minimal changes were observed with placebo. DSMB review did not identify any confirmed cases of DILI or any liver adverse events related to study drug.