VANTAGE: Promising data of volixibat in cholestatic pruritus

Treatment with the investigational agent volixibat was associated with clinically relevant reductions in primary biliary cholangitis-associated cholestatic pruritus. The encouraging results of the phase 2b study support further investigation of volixibat in larger clinical trials.

“Cholestatic pruritus is a debilitating symptom of primary biliary cholangitis that has a large impact on patients’ quality-of-life,” explained Dr Kris Kowdley (Liver Institute Northwest, WA, USA) [1]. Volixibat is an ileal bile acid transporter inhibitor, blocking the enterohepatic recirculation of bile acids, resulting in lower serum bile acid concentrations. “Since elevated serum bile acid levels have been associated with cholestatic pruritus, volixibat may be effective in reducing cholestatic pruritus,” said Dr Kowdley. The phase 2b VANTAGE study (NCT05050136) randomised patients with primary biliary cholangitis and cholestatic pruritus 1:1:1 to volixibat 20 mg, volixibat 80 mg, or placebo, twice daily for all. The primary endpoint was the mean change in adult itchRO score at week 28. Dr Kowdley presented the findings of an interim analysis, including 31 participants.

Participants in the combined volixibat arms showed a placebo-adjusted reduction of 2.51 points in adult ItchRO score (P=0.0005). “The volixibat doses yielded comparable responses,” according to Dr Kowdley. Furthermore, about 70% of the participants on volixibat reached a reduction in serum bile acids of at least 50%. Dr Kowdley also mentioned that there was an improvement in fatigue among participants who were being treated with volixibat. Lastly, the most common adverse event in the experimental groups was diarrhoea. “Fortunately, all side effects we observed were mild in severity,” he added.

Volixibat induced significant reductions in cholestatic pruritus associated with primary biliary cholangitis in the current phase 2b study. The investigators will proceed with the 20 mg dose to further evaluate this novel therapy.

1. Kowdley K, et al. Volixibat for the treatment of cholestatic pruritus in primary biliary cholangitis: ad adaptive, randomized, placebo-controlled phase 2b trial (VANTAGE): interim results. Abstract 784, Digestive Disease Week 2025, 3–6 May 2025, San Diego, USA.

Copyright ©2025 Medicom Medical Publishers



Posted on 21 May 202526 September 2025