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The regulatory action is based on a positive preliminary analysis of the VANTAGE trial.
The FDA announced the granting of a breakthrough therapy designation to volixibat, an oral ileal bile acid transporter (IBAT) inhibitor, as a possible treatment for cholestatic pruritus in patients with primary biliary cholangitis (PBC), according to a news release from Mirum Pharmaceuticals.1
Primary biliary cholangitis can cause cholestatic pruritus. | Image credit: © syahrir | stock.adobe.com
The designation is based on the positive interim analysis of the phase 2b VANTAGE (NCT05050136) study, which found that volixibat demonstrated a statistically significant (-3.82, p < .0001) improvement in pruritus. Furthermore, 75% of patients receiving volixibat achieved a greater than 50% reduction in serum bile acids with improvements in fatigue at week 16 also observed.1,2
Safety signals for volixibat were positive, and no novel safety signals were observed. Adverse events (AEs) were similar between both the 20 mg and 80 mg treatment groups, with the most common AE being diarrhea (77%). All cases were mild to moderate and mostly transient, though 1 case resulted in discontinuation of the trial. In total, 4 patients experienced serious AEs, including 1 patient in the placebo arm.2
Confirmatory portions of the trial are ongoing, with enrollment completion expected in 2026. This new designation will allow for the development and review of volixibat to be expedited, with the preliminary evidence indicating positive impacts of the treatment.1
“Breakthrough therapy designation for volixibat in PBC underscores the importance and urgency for a treatment to address one of the most burdensome impacts of this rare liver disease,” Joanne Quan, MD, chief medical officer at Mirum, said in the news release. “We look forward to advancing our VANTAGE study with the goal of making volixibat available to patients living with PBC-related itch as quickly as possible.”1
Volixibat, called SHP626, previously received fast track designation from the FDA in 2016 for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) in patients with liver fibrosis. The once daily, orally administered inhibits the apical sodium dependent acid transporter, a protein that is primarily responsible for recycling bile acids from the intestine to the liver.3
Trial Name: A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis (VANTAGE)
ClinicalTrials.gov ID: NCT05050136
Sponsor: Mirum Pharmaceuticals Inc
Completion Date (Estimated): December 2025
The positive results observed in patients with MASH provide a hopeful indication that volixibat can lead to similarly strong results in patients with PBC, another disease that seriously impacts the liver.3
By blocking the recycling of these bile acids through inhabitation of ileal bile acid transporter, volixibat could offer a new approach in the treatment of adults with cholestatic diseases. In addition to the ongoing VANTAGE study, volixibat is currently being evaluated in trials for the treatment of primary sclerosing cholangitis.1
“The symptomatic burden in PBC is significant and often an underappreciated aspect of this disease. Both itch and fatigue are devastating hallmarks of PBC that can significantly decrease quality of life,” Carol Roberts, president of the PBCers Organization, said in the news release announcing the positive preliminary trial results in June. “It is incredibly encouraging for PBC patients to see such promising results with volixibat.”2
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