Heubi JE, et al. – The efficacy and safety of oral cholic acid were examined in patients with bile acid synthesis disorders (BASDs). Results confirmed that oral cholic acid was a safe, efficacious, and well–tolerated treatment option for BASD due to single enzyme defects (SED) and Zellweger spectrum disorders (ZSDs).

Methods

• In this study, patients were administered cholic acid orally 10 to 15 mg · kg^–1 · day^–1.
• The primary efficacy variables were changes from pre– to post–treatment in atypical urinary bile acids, liver chemistries (serum aspartate aminotransferase, alanine aminotransferase), and height and weight.
• Additional efficacy variables included changes in serum bilirubin and liver histology.

Results

• Out of 85 enrolled patients (63 with SED and 22 with ZSD), 79 received at least 1 dose of study medication.
• 70 patients (50 with SED and 20 with ZSD) were included in the modified intent–to–treat dataset.
• In patients with SED and ZSD, cholic acid significantly improved urine bile acid metabolite scores (P < 0.0001) and serum aspartate aminotransferase and alanine aminotransferase (P < 0.0001) in patients with SED and ZSD.
• Cholic acid also improved height and weight percentiles in both groups, but only the change in weight was significant (P < 0.05).
• Serum direct bilirubin decreased significantly post–treatment (P < 0.001) in the intent-to-treat population, and liver biopsies showed either stable findings or histologic improvement in all parameters except bridging fibrosis.
• The overall safety profile of cholic acid was favorable, with no study drug–related serious adverse events or drug–related deaths reported.