Twice-daily volixibat shows clear results for itch relief in PSC in trial
Developer planning to seek drug's approval by year's end, schedules FDA meet
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Twice-daily treatment with volixibat, Mirum Pharmaceuticals’ oral investigational therapy for primary sclerosing cholangitis (PSC) significantly outperformed a placebo in reducing moderate to severe itch, medically known as pruritus, in people with the rare, chronic liver condition.
That’s according to new top-line data from the ongoing VISTAS clinical trial (NCT04663308), which is testing the drug against the placebo in more than 150 PSC patients. The findings, which will be presented at an international scientific congress by the end of the month, mean that the Phase 2b trial has met its primary goal, Mirum announced in a company press release detailing the data.
The company has scheduled a meeting with the U.S. Food and Drug Administration this summer to discuss an application seeking volixibat’s U.S. approval, with a planned submission by the end of the year.
“In a disease that has been historically difficult to study and treat, VISTAS delivered a clear and compelling efficacy signal,” said Joanne Quan, MD, Mirum’s chief medical officer. “The observed statistically significant and clinically meaningful reductions in pruritus demonstrate the potential for volixibat to address one of PSC’s most burdensome and defining symptoms.”
Trial participants completing the placebo-controlled part of VISTAS could enroll in its open-label extension portion, where all are receiving volixibat long term.
In PSC, the tubes that carry the digestive fluid bile inside the liver and/or outside the liver to the intestines become inflamed, a condition called cholangitis. As these tubes, or bile ducts, become blocked, bile builds up in the liver, causing damage that can eventually lead to liver failure. Bile also leaks into the bloodstream, leading to symptoms such as pruritus.
“Cholestatic pruritus is one of the most common symptoms in PSC, which remains a challenging disease to manage,” said Kris Kowdley, MD, a VISTAS investigator, the director of the Liver Institute Northwest, and a professor at Washington State University’s Elson S. Floyd College of Medicine. “In clinical practice, we have very limited options to effectively address this symptom.”
For many with PSC, itch is ‘constant and deeply disruptive’
Ricky Safer, founder and CEO of the advocacy organization PSC Partners Seeking a Cure, explained the impact of pruritus on those with PSC: “For many patients, the itch associated with PSC is constant and deeply disruptive — affecting sleep, daily activities and overall quality of life.”
Given as oral capsules, volixibat is designed to block a gut protein called IBAT, fully, ileal bile acid transporter. IBAT is responsible for recycling bile acids, bile’s main component, from the intestines back into the liver. By interrupting this process, volixibat aims to increase bile acid excretion in stools, lowering bile levels in the liver and bloodstream, and slowing liver damage and relieving symptoms.
VISTAS evaluated the safety and efficacy of volixibat (20 mg), given twice daily, against a placebo in 158 people with PSC with moderate to severe itch. Patients were divided into two groups based on their level of itch at the study’s start, as measured by the Adult ItchRO scale. The primary analysis group covered the 111 participants with moderate to severe itch, while the secondary group involved the 47 participants with mild itch.
The trial’s main goal was to measure the mean score change in the Adult ItchRO scale from the start of the study to the average of the last 12 weeks, or three months, of treatment.
An interim analysis conducted when 42 participants completed a four-month assessment prompted an independent data review committee to conclude that VISTAS should continue as planned with the 20 mg volixibat dose.
Treatment with volixibat eased itch in as little as 2 weeks
The newly announced top-line data show that, in the primary analysis group, use of volixibat led to a significantly greater mean score drop on the ItchRO scale relative to the placebo (2.72 vs. 1.08 points). Also, a significantly greater proportion of volixibat-treated patients experienced a reduction of at least two points (56% vs. 26%).
Volixibat also reduced blood bile acid levels, with volixibat-treated patients showing a mean reduction of 33.7 units, while those on the placebo had a slight mean increase of 2.1 units.
Reductions in itch were observed as early as two weeks after starting treatment, and significant reductions in itch scores were also seen in the secondary group of patients.
After decades of commitment from patients, families and researchers participating in PSC studies, these results represent real hope for what could become the first approved treatment. … Seeing meaningful progress in reducing [disruptive itch] is incredibly encouraging for a community that has long had limited options.
The therapy’s safety profile was generally consistent with the known effects of IBAT blockage, including gastrointestinal problems and elevations in liver enzymes. Adverse events occurred slightly more often with volixibat than the placebo (93.5% vs. 84%), and study discontinuation due to adverse events was higher in the volixibat group (9.1% vs. 2.5%), most commonly due to diarrhea.
“After decades of commitment from patients, families and researchers participating in PSC studies, these results represent real hope for what could become the first approved treatment,” Safer said. “Seeing meaningful progress in reducing this burden is incredibly encouraging for a community that has long had limited options.”
Mirum is also evaluating volixibat in adults with itch due to primary biliary cholangitis (PBC), a related disease, in the similarly designed Phase 2b VANTAGE trial (NCT05050136). Top-line results from that study are expected in the first months of 2027.
