Volixibat Shows Rapid Itch Relief in PSC in Phase 2b VISTAS, With Kris Kowdley, MD

Cholestatic pruritus in primary sclerosing cholangitis (PSC) has historically received less attention than other complications of the disease, despite growing evidence that itch can substantially impair quality of life. New phase 2b data from the VISTAS trial suggest volixibat, an investigational ileal bile acid transporter (IBAT) inhibitor, may offer a meaningful and fast-acting treatment option for patients with few alternatives beyond off-label therapies.

In discussing the findings with HCPLive, study investigator Kris Kowdley, MD, director at Liver Institute Northwest and senior scientific advisor and medical director at Velocity Clinical Research, emphasized that pruritus in PSC may be substantially more burdensome than historically appreciated.

Generally, PSC has not been viewed as a pruritus-dominant disease in the way that primary biliary cholangitis (PBC) has. Thus, emerging evidence suggests itch may be more common and clinically significant than previously appreciated. A patient-reported survey of > 400 individuals with PSC found that > 90% reported itch at some point in their lives. A separate European study using objective pruritus measures found approximately 25% of patients had moderate-to-severe itch.1,2

Pruritus in cholestatic liver disease has been associated with impaired sleep, fatigue, reduced functional status, and social withdrawal. In PSC, symptom burden may worsen acutely during episodes of cholangitis or bile duct strictures, adding further complexity to disease management. Despite this, no therapies are currently approved in the United States specifically for PSC-associated pruritus.2,3

VISTAS Met Primary Endpoint for PSC-Associated Pruritus

According to topline company-reported results, volixibat 20 mg twice daily produced a least squares mean change in Adult ItchRO score of −2.72 versus −1.08 with placebo, yielding a placebo-adjusted difference of −1.64 (P <.0001).

“The fact that this was a large study, carefully designed and adequately controlled with placebo, showing a meaningful reduction in itch score using the ItchRO assessment and associated with reduction in bile acids, all of these suggest that this may be a valuable therapy for patients with PSC to relieve symptoms,” explained Kowdley.

Safety Findings Consistent With IBAT Inhibition

Safety findings were described as generally consistent with IBAT inhibition. Across study cohorts, treatment-emergent adverse events occurred in 93.5% of patients receiving volixibat and 84.0% receiving placebo. Diarrhea-related discontinuation occurred in 3.9% versus 1.2%, respectively, and the company also reported elevations in alanine aminotransferase and bilirubin.1

Tolerability may be particularly relevant in PSC, where many patients also have inflammatory bowel disease, and gastrointestinal adverse events may carry additional clinical implications.

Rapid Symptom Relief May Carry Particular Importance in PSC

The company reported improvements in pruritus within 2 weeks of treatment initiation, although detailed time-course data have not yet been presented publicly.1 Rapid symptom improvement is especially meaningful in PSC, where disease-modifying therapies remain limited and chronic itch can substantially impair quality of life.

“For patients that have been suffering from cholestatic pruritus for months or years, it’s very gratifying to see this prompt symptom relief,” Kowdley said.

Full results from VISTAS are expected at the European Association for the Study of the Liver International Liver Congress on May 30, 2026.1 Mirum said a pre–new drug application meeting with the FDA is planned for summer 2026, with a potential submission in the second half of the year.1

Editor’s Note: Kowdley reports relevant disclosures with Akero, 89Bio, Boehringer Ingelheim, Boston Pharmaceuticals, Genfit, Gilead, GlaxoSmithKline, Intercept, Madrigal, Mirum, and others.

References

1. Mirum Pharmaceuticals. Mirum Pharmaceuticals announces primary endpoint met in VISTAS study of volixibat in patients with primary sclerosing cholangitis. News release. May 4, 2026. Accessed May 13, 2026. https://www.businesswire.com/news/home/20260504069726/en/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-VISTAS-Study-of-Volixibat-in-Patients-with-Primary-Sclerosing-Cholangitis

2. Hov JR, Boberg KM, Karlsen TH. Health-related quality of life in primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol. 2012;36(1):40-47. doi:10.1016/j.clinre.2011.08.007

3. Benito de Valle M, Rahman M, Lindkvist B, et al. Factors associated with pruritus in patients with primary sclerosing cholangitis. Liver Int. 2021;41(12):2896-2904. doi:10.1111/liv.15044

4. Bowlus CL, Lim JK, Lindor KD. AGA clinical practice update on surveillance for hepatobiliary cancers in primary sclerosing cholangitis: expert review. Gastroenterology. 2019;157(3):769-775. doi:10.1053/j.gastro.2019.07.055

5. Gunaydin M, Bozkurt Y, Demirci H, et al. Ileal bile acid transporter inhibitors in cholestatic pruritus and cholestatic liver disease: current evidence and future directions. Clin Res Hepatol Gastroenterol. 2024;48(1):102271. doi:10.1016/j.clinre.2023.102271