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Volixibat reduced cholestatic pruritus in phase 2b primary sclerosing cholangitis data, with diarrhea and liver test elevations reported.
Mirum Pharmaceuticals reported volixibat met the primary endpoint in the phase 2b VISTAS trial in adults with primary sclerosing cholangitis (PSC) and cholestatic pruritus, a symptom with limited treatment options and no approved PSC-specific therapies in the US.1
The company said the investigational ileal bile acid transporter (IBAT) inhibitor produced a statistically significant placebo-adjusted reduction in itch severity over 28 weeks, in their May 4, 2026 announcement.
“In PSC, a disease that has been historically difficult to study and treat, volixibat delivered statistically significant and clinically meaningful reductions in cholestatic pruritus,” Joanne Quan, MD, chief medical officer at Mirum, said in the company’s announcement.1 The topline readout is likely to draw attention because pruritus is a major driver of impaired quality of life in PSC, a chronic cholestatic liver disease that can progress to cirrhosis, liver failure, cholangiocarcinoma, and transplantation.2,3
According to the press release, VISTAS was a global, randomized, double-blind, placebo-controlled phase 2b study enrolling 158 patients with PSC.1 Patients were stratified into a primary analysis cohort with moderate to severe itch at baseline (n = 111) and a secondary cohort with mild itch (n = 47), based on Adult Itch Reported Outcome (ItchRO) scores. The prespecified primary endpoint was assessed in the moderate-to-severe pruritus cohort.
In that cohort, patients assigned to volixibat 20 mg twice daily had a least squares mean change in Adult ItchRO score of −2.72 vs −1.08 with placebo, for a placebo-adjusted difference of −1.64 (P < .0001).1 Mirum also reported that 55.6% of volixibat-treated patients achieved at least a 2-point reduction in Adult ItchRO score compared with 26.3% in the placebo group (P = .0019).1 Serum bile acids also decreased relative to placebo, with a least squares mean difference of −35.8 (P = .0324).1 The company said improvements in pruritus were observed within 2 weeks, although full data have not yet been presented publicly.
Safety findings were described as generally consistent with IBAT inhibition.1 Across the primary and secondary cohorts, treatment-emergent adverse events occurred in 93.5% of patients receiving volixibat and 84.0% receiving placebo; grade 3 or higher events occurred in 13.0% and 11.1%, respectively.1 Serious treatment-emergent adverse events were reported in 10.4% vs 6.2%, and study discontinuation due to adverse events occurred in 9.1% vs 2.5%.1 Diarrhea-related discontinuation was reported in 3.9% of volixibat-treated patients and 1.2% of placebo recipients.1 The company also noted elevations in alanine aminotransferase and bilirubin.
PSC remains an area of substantial unmet need. Major liver society guidance notes that no medical therapy has been conclusively shown to alter long-term disease course, and management is largely supportive, addressing dominant strictures, inflammatory bowel disease, surveillance for hepatobiliary malignancy, and symptom control.2,3 Pruritus is commonly managed with off-label approaches such as bile acid sequestrants, rifampin, opioid antagonists, and selective serotonin reuptake inhibitors, but tolerability and efficacy are variable.2
Volixibat belongs to the same broad drug class as maralixibat and odevixibat, IBAT inhibitors already approved for pruritus in certain pediatric cholestatic disorders.4 By reducing enterohepatic bile acid recirculation, these agents may lessen systemic bile acid exposure and cholestatic itch. Whether this mechanism will translate into a favorable benefit-risk profile in PSC, where liver biochemistry fluctuations and disease heterogeneity complicate interpretation, will depend on fuller disclosure of trial details.
For clinicians, the main significance of the VISTAS readout is symptomatic rather than disease-modifying. The reported effect size on ItchRO appears potentially relevant for patients with burdensome itch, but the absence of peer-reviewed data, subgroup analyses, and detailed laboratory outcomes limits interpretation. It also remains unclear how regulators will weigh a pruritus endpoint in PSC, especially in the setting of liver test elevations and higher discontinuation rates.
Mirum said a pre–new drug application meeting with the FDA is planned for summer 2026, with a possible submission in the second half of the year.1 Full results are expected at the European Association for the Study of the Liver International Liver Congress on May 30, 2026.1 Those data should help clarify durability of response, safety over time, and whether any patient subgroups derived greater benefit.
