Mirum Pharmaceuticals (Nasdaq: MIRM) reported that volixibat met the primary endpoint in the Phase IIb VISTAS study, producing a statistically significant reduction in cholestatic pruritus in patients with primary sclerosing cholangitis — a disease for which no approved therapy currently exists.
The VISTAS study is a global, randomized, double-blind, placebo-controlled Phase IIb trial evaluating volixibat 20 mg twice daily in 158 patients with cholestatic pruritus caused by PSC, stratified by itch severity at baseline into a primary cohort (moderate to severe itch; n=111) and a secondary cohort (mild itch; n=47).
In the primary analysis cohort, volixibat produced a least-squares mean reduction of 2.72 points on the Adult Itch Reported Outcome scale versus 1.08 points with placebo, a placebo-adjusted difference of 1.64 points (p<0.0001). A clinically interpretable responder analysis reinforced that signal: 55.6% of volixibat-treated patients achieved at least a 2-point reduction in itch score, compared with 26.3% on placebo (p=0.0019). Serum bile acids, a pharmacodynamic marker of IBAT inhibition, fell by a mean of 33.7 units with volixibat versus a rise of 2.1 units with placebo (p=0.0324). Mirum also noted that pruritus improvements emerged within two weeks of treatment initiation.
Volixibat is an oral, minimally absorbed inhibitor of the ileal bile acid transporter (IBAT/ASBT; SLC10A2), which mediates reuptake of bile acids from the terminal ileum back into portal circulation. By blocking that transporter, volixibat increases fecal bile acid excretion and reduces the circulating bile acid pool — the same core mechanism underlying maralixibat (Livmarli), Mirum's approved IBAT inhibitor for pediatric cholestatic conditions. The rationale for applying that mechanism to PSC-associated pruritus rests on evidence that elevated bile acid levels contribute to the itch burden in cholestatic liver disease, though the precise pruritogenic pathway remains incompletely characterized.
PSC affects an estimated 30,000 patients in the United States and carries a heavy symptom burden alongside its progressive structural damage to the bile ducts. Pruritus is among the most frequent and disabling complaints, yet the treatment landscape has been effectively empty: no drug carries FDA approval for any aspect of PSC management, and clinicians have relied on off-label agents including rifampicin, naltrexone, and cholestyramine with inconsistent results. That regulatory vacuum makes the VISTAS study results consequential for the field, even at Phase IIb scale.