Cholic Acid Sustains Efficacy, Safety in Long-Term Treatment of BASDs
Cholic acid treatment downregulates production of atypical bile acids and improves liver biochemistries and growth in patients with bile acid synthesis disorders (BASDs), including both single-enzyme defects (SEDs) or Zellweger spectrum disorders (ZSDs), according to results from a new study.
The researchers also determined that the safety and efficacy of cholic acid for treating BASD were sustained over the long term and that the treatment showed potential for additional improvement in certain efficacy parameters.
BASDs impair the primary pathway of bile acid synthesis and lead to reduced primary bile acids, upregulated synthesis of cholesterol, and production and accumulation of hepatotoxic atypical bile acids.
In this phase 3, open-label, single-arm study, the researchers performed efficacy assessments, which included urinary atypical bile acids, serum liver chemistries, body weight, and height. Of the 53 total participants (SED, n=41; ZSD, n=12), 22 were treatment-naïve and 31 were taking cholic acid from a previous study. The mean age of the participants at diagnosis was 55 months and at baseline of the present study was 9 years.
The results showed statistically significant improvements in urinary bile acids, height, and body weight. Serum alanine aminotransferase and aspartate aminotransferase levels decreased from baseline among treatment-naïve participants following cholic acid treatment and remained stable in previously treated participants. Treatment-naïve participants improved in all baseline-to-best postbaseline analyses. The most common treatment-emergent adverse event was upper respiratory tract infection (17%).
“The findings from this study demonstrate that oral cholic acid treatment downregulates bile acid synthesis and production of atypical bile acids, with concomitant improvements in serum liver biochemistries, and is safe and efficacious for short- and long-term therapy for patients with inborn errors of bile acid synthesis,” the researchers concluded.
—Rebecca Mashaw
Reference:
Heubi JE, Setchell KDR. Open-label phase 3 continuation study of cholic acid in patients with inborn errors of bile acid synthesis. J Pediatr Gastroenterol Nutr. 2020;70(4):423-429.