Abstract
OBJECTIVES: This study aimed to assess the safety and efficacy of cholic acid (CA) treatment over 74 weeks in Japanese patients with inherited enzymatic bile acid synthesis disorders (BASD). METHODS: This phase 3, open-label, single-arm study enrolled four Japanese patients diagnosed with BASD, including two with 3β-hydroxy-Δ (5)-C(27)-steroid dehydrogenase/isomerase (HSD3B7) deficiency and two with Δ (4)-3-oxosteroid 5β-reductase (SRD5B1) deficiency. The patients had received chenodeoxycholic acid (CDCA) treatment but were switched to CA treatment. Treatment efficacy was evaluated by measuring serum and urinary bile acid levels and liver-related biomarkers, and adverse events were evaluated to monitor safety. RESULTS: The daily CA doses ranged from 3.8 to 13.7 mg/kg/day. Laboratory values of liver-related biomarkers were maintained within normal ranges or improved. Bile acid analysis revealed CDCA replacement with CA in serum within the initial few weeks of CA treatment. Urinary concentrations of toxic bile acid metabolites associated with liver damage were higher than serum. Adverse effects from CA treatment were mild to moderate, and no treatment discontinuations were due to adverse events. CONCLUSIONS: CA treatment over 74 weeks resulted in favorable efficacy and safety outcomes in Japanese patients with BASD, consistent with previous studies. These results support the utility of CA as a therapeutic option for Japanese patients with BASD.