Volixibat Improves Fatigue and Sleep in Patients With Primary Biliary Cholangitis

New research is shedding light on improved clinical outcomes of pruritus symptoms in adults with primary biliary cholangitis (PBC) treated with volixibat, showing meaningful improvements in fatigue and sleep disturbances.1

Findings from the phase 2b VANTAGE trial were presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025 by Kris Kowdley, MD, director of the Liver Institute Northwest, and demonstrate a potential link between effective management of cholestatic itch and improvements in energy and sleep quality among adults with PBC.

“Treatment with VLX in the completed Part 1 (dose selection) of the VANTAGE study showed statistically significant and clinically relevant improvements in pruritus. Here, we explore the impact of VLX on fatigue and sleep in PBC,” wrote Kowdley and colleagues.

PBC, a rare, autoimmune, cholestatic liver disease, has shown a gradual increase in prevalence, with roughly 18.1 cases per 100,000 individuals. The associated healthcare and disease burden continues to grow, underscoring the need for innovative approaches to improve patient outcomes. Previous studies have found patients with moderate-to-severe pruritus, described as a debilitating itch, experience substantial reductions in health-related quality of life (HRQoL).2

In October 2024, the US Food and Drug Administration granted Breakthrough Therapy Designation to volixibat, underscoring the need for a treatment to reduce pruritus symptoms and their healthcare impacts. Volixibat is a minimally absorbed ileal bile acid transporter inhibitor which blocks the enterohepatic recirculation of bile acids. The designation was supported by results from VANTAGE highlighting meaningful change in daily itch scores, alkaline phosphatase, total bilirubin, serum bile acid levels, and HRQoL compared with placebo.3

VANTAGE is a 28-week randomized, multicenter, double-blind, placebo-controlled phase 2b, study designed to evaluate the effect of volixibat on pruritus symptoms in adults with PBC. In Part 1, patients were randomized in a 1:1:1 ratio to receive placebo or volixibat, 20 mg or 80 mg. Part 2 is an ongoing confirmatory period utilizing the reported trial data on fatigue and sleep. The data will be assessed by a PBC-specific HRQoL questionnaire (PBC-40) and a Patient-Reported Outcomes Measurement Information System (PROMIS).

In VANTAGE, 31 participants with moderate-to-severe pruritus were randomly assigned to placebo (n = 11) or volixibat (n = 20). Volixibat-treated patients showed greater improvement (least squares mean [SE]) in fatigue and sleep scores compared with placebo. Fatigue improved by –4.2 (1.7) on the PBC-40 and –3.8 (1.9) on the PROMIS Fatigue scale versus –2.4 (2.8) and –0.9 (3.2), respectively, for placebo. Sleep disturbance scores improved by –4.3 (1.8) with volixibat and –0.9 (3.3) with placebo.

Nearly half of volixibat-treated participants (47%) achieved a ≥3-point improvement in PROMIS Fatigue scores, compared with 17% on placebo. By week 28, most volixibat-treated patients reported normal or mild fatigue and sleep disturbance, with minimal changes in the placebo group.

“VANTAGE Part 1 results support the hypothesis that efficacious pruritus treatment with VLX may result in improvements in sleep and fatigue in PBC,” wrote Kowdley. “Improvements in fatigue and sleep will be further evaluated in the ongoing Part 2 period of the VANTAGE study.”

References

1. Kowdley K, Shiffman M, Weinstein D, et al. Volixibat leads to improvements in fatigue and sleep for adults with primary biliary cholangitis: Data from VANTAGE. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

2. Levy C, Younossi ZM, Mayo MJ, et al. Assessment of PBC Pruritus from the ITCH ‐E Study: Quality of Life, Productivity, and Treatment Experiences. Liver International 2025, 45 (9). https://doi.org/10.1111/liv.70276

3. Brooks, A. FDA Grants Breakthrough Therapy Designation to Volixibat for Cholestatic Pruritus in PBC. HCPLive. October 10, 2024. Accessed November 7, 2025. https://www.hcplive.com/view/fda-grants-breakthrough-therapy-designation-volixibat-cholestatic-pruritus-pbc