Itch Relief With Volixibat Tied to Better Sleep, Fatigue in PSC

Volixibat, an investigational ileal bile acid transporter (IBAT) inhibitor, improved sleep compared with placebo in adults with primary sclerosing cholangitis (PSC) and cholestatic pruritus, according to new data from the phase 2b VISTAS trial.¹

Christopher Bowlus, MD, of the University of California Davis, presented the analysis at The Liver Meeting 2026, hosted by the American Association for the Study of Liver Diseases (AASLD), in Denver, Colorado.

Results showed participants with a pruritus response also reported greater improvements in fatigue and sleep, regardless of treatment assignment.¹

While no therapies are currently approved for PSC, VISTAS met its primary endpoint, with a least squares (LS) mean reduction in Adult ItchRO score of 2.72 points with volixibat compared with 1.08 points with placebo (difference, −1.64; P < .001).² The new analysis examined whether itch relief with volixibat extends to other patient-reported symptoms.

How Did Volixibat Affect Sleep and Fatigue in VISTAS?

VISTAS is a 28-week, randomized, multicenter, double-blind, placebo-controlled phase 2b study in adults with PSC and cholestatic pruritus. The primary cohort included 111 participants with moderate to severe pruritus, randomized to volixibat 20 mg twice daily (n = 54) or placebo twice daily (n = 57). Investigators assessed fatigue and sleep through Week 28 using validated Patient-Reported Outcomes Measurement Information System (PROMIS) health-related quality of life measures, analyzed with a mixed model for repeated measures.¹

Results showed sleep improved significantly more with volixibat than with placebo, with an LS mean change of −6.47 (SE, 1.3) compared with −0.78 (SE, 1.2) (P = .0011).¹ Negative changes in PROMIS scores indicate improvement.

In VISTAS data presented at the American College of Gastroenterology (ACG) 2026 meeting, the difference in PROMIS fatigue scores between volixibat and placebo (−2.33) did not reach statistical significance (P = .13).² The new analysis instead examined fatigue through the lens of itch response.

Do Itch Responders See Greater Gains in Fatigue and Sleep?

Investigators compared outcomes between pruritus responders, defined as a reduction of at least 2 points in Adult ItchRO score, and nonresponders, irrespective of treatment assignment. In earlier VISTAS data, 56% of volixibat-treated participants met this threshold, compared with 26% of placebo-treated participants (P = .002).² Responders reported greater improvement than nonresponders in fatigue (mean change, −6.25 [SD, 7.8] vs −0.34 [SD, 6.3]; P = .0004) and sleep (−7.48 [SD, 9.5] vs 0.18 [SD, 6.6]; P < .0001).¹

Among responders, the magnitude of improvement was larger with volixibat than with placebo. The difference reached statistical significance for sleep (−10.20 vs −2.93; P = .0165) but not for fatigue (−7.03 vs −4.95; P = .41). The authors concluded improvements in pruritus were associated with improvements in fatigue and sleep, with greater gains following volixibat treatment.¹

Across both VISTAS cohorts, diarrhea occurred in 40.3% of volixibat-treated participants vs 8.6% of placebo-treated participants, and adverse events led to discontinuation in 9.1% versus 2.5%, respectively. Elevations in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin were more frequent with volixibat.²

In August 2026, the FDA granted volixibat Breakthrough Therapy and Orphan Drug designations for cholestatic pruritus due to PSC.³ After a pre-New Drug Application (NDA) meeting in which the FDA recommended an additional phase 3 study, Mirum Pharmaceuticals said it plans further discussions with the agency and a potential NDA submission in the first half of 2027.³ Volixibat is also under evaluation in primary biliary cholangitis in the phase 2b VANTAGE trial.²

References

1. Bowlus C, Levy C, Shiffman M, et al. The impact of volixibat, an IBAT inhibitor, on fatigue and sleep for patients with primary sclerosing cholangitis: data from VISTAS. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Brooks A. Volixibat reduces PSC-related pruritus in phase 2b VISTAS trial. HCPLive. Published October 12, 2026. Accessed November 5, 2026. https://www.hcplive.com/view/volixibat-reduces-psc-related-pruritus-in-phase-2b-vistas-trial

3. Hillenbrand A. FDA grants volixibat Breakthrough Therapy, Orphan designations for PSC. HCPLive. Published August 10, 2026. Accessed November 5, 2026. https://www.hcplive.com/view/fda-grants-volixibat-breakthrough-therapy-orphan-designations-for-psc