Volixibat Reduces PSC-Related Pruritus in Phase 2b VISTAS Trial

Volixibat, an investigational ileal bile acid transporter (IBAT) inhibitor, significantly reduced cholestatic pruritus vs placebo in patients with primary sclerosing cholangitis (PSC) and moderate to severe itch in the phase 2b VISTAS trial. Mitchell Shiffman, MD, of the Liver Institute of Virginia, Bon Secours Mercy Health, presented the results at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.1

PSC has no approved pharmacologic therapies, and pruritus and fatigue substantially impair patients’ quality of life.1 Investigators described VISTAS as the largest interventional study of an IBAT inhibitor in PSC and the first controlled evidence of a potential therapy addressing the cholestatic symptom burden in the disease.1

VISTAS Phase 2b Trial Design and Patient Population

VISTAS was a 28-week, multicenter, randomized, double-blind, placebo-controlled trial. It enrolled participants aged 12 years or older with PSC diagnosed per American Association for the Study of Liver Diseases guidelines. Concomitant inflammatory bowel disease (IBD) was permitted if treatment was stable.1,3

The primary efficacy cohort included 111 participants with moderate to severe pruritus, randomly assigned in a 1:1 ratio to oral volixibat 20 mg twice daily (n = 54) or placebo (n = 57). Another 47 participants with mild pruritus formed a secondary cohort. Safety was assessed in all 158 participants.1

Mean baseline Adult Itch-Reported Outcome (ItchRO) scores, measured on a 0-to-10 scale, were 6.3 with volixibat and 6.1 with placebo. Roughly three-quarters of each group had IBD. The primary end point was change in Adult ItchRO score from baseline to the average of the last 12 weeks of treatment.1

Volixibat Pruritus, Bile Acid, and Sleep Outcomes

Adult ItchRO scores decreased by a least-squares mean of 2.72 points with volixibat vs 1.08 points with placebo, a difference of −1.64 points (P <.001). Separation from placebo emerged as early as week 2 and persisted through week 28.1

More patients receiving volixibat achieved a reduction of at least 2 points (56% vs 26%; P = .002). Mirum Pharmaceuticals, the trial sponsor, also reported a reduction of ≥ 3 points in 37% vs 11% of patients (P = .001).1,2

Serum bile acid levels fell by 33.7 µmol/L with volixibat and rose by 2.1 µmol/L with placebo (difference, −35.8 µmol/L; P = .03). Baseline levels were higher in the volixibat group (109.6 vs 61.4 µmol/L). On the Patient-Reported Outcomes Measurement Information System, sleep disturbance scores improved more with volixibat (difference, −5.69; nominal P = .001). The difference in fatigue scores (−2.33) was not statistically significant (P = .13).1

Volixibat Safety Findings in PSC

Treatment-emergent adverse events (TEAEs) occurred in 93.5% of participants receiving volixibat and 84.0% receiving placebo. Of these, 44.2% and 19.8%, respectively, were considered treatment related. Grade 3 or higher TEAEs occurred in 13.0% and 11.1%.1

The most common TEAEs with volixibat were diarrhea (40.3% vs 8.6%), abdominal pain (18.2% vs 9.9%), and nausea (13.0% vs 3.7%). Vitamin D deficiency was reported in 10.4% vs 4.9%. TEAEs led to discontinuation in 9.1% vs 2.5% of participants, including 3 and 1 discontinuations for diarrhea, respectively.1

Serious TEAEs occurred in 10.4% and 6.2%, and none were considered treatment related. Elevations in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin were more frequent with volixibat. One death, from spontaneous bacterial peritonitis, occurred in the placebo group. Investigators described the safety profile as generally consistent with known effects of IBAT inhibition.1

IBAT Inhibitor Background and Next Steps for Volixibat

Volixibat is a minimally absorbed oral agent that blocks bile acid reuptake in the ileum. This interrupts enterohepatic recirculation and reduces the bile acid pool implicated in cholestatic pruritus.1,2 Maralixibat, another IBAT inhibitor, is approved in the US for cholestatic pruritus in Alagille syndrome and progressive familial intrahepatic cholestasis. Volixibat is also being studied in primary biliary cholangitis in the phase 2b VANTAGE trial.2

Mirum has stated plans to submit a New Drug Application for volixibat in PSC in the second half of 2026.1,2

References

1. Levy C, Hirschfield GM, Shiffman M, et al. Efficacy and safety of volixibat, an IBAT inhibitor, in patients with primary sclerosing cholangitis and moderate-to-severe pruritus: results of the VISTAS trial. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. Mirum Pharmaceuticals announces new data from rare liver disease programs presented at the EASL International Liver Congress 2026. News release. Mirum Pharmaceuticals; 2026. Accessed October 12, 2026. https://www.businesswire.com/news/home/20260530475386/en/

3. A study to evaluate efficacy and safety of an investigational drug named volixibat in patients with itching caused by primary sclerosing cholangitis (PSC) (VISTAS). ClinicalTrials.gov identifier: NCT04663308. Updated February 4, 2026. Accessed October 12, 2026. https://clinicaltrials.gov/study/NCT04663308