The U.S. Food and Drug Administration has granted breakthrough therapy designation to volixibat, developed by Mirum Pharmaceuticals, as a potential treatment for cholestatic pruritus (itching) in patients with primary biliary cholangitis (PBC), the company announced recently in a press release.
Breakthrough therapy designation is a special process for experimental drugs with preliminary results from clinical trials suggesting a significant improvement over previously available therapies. Developers expect that the designation will help expedite the development process.
What is PBC?
Primary biliary cholangitis (PBC) is a rare, chronic autoimmune disease that primarily affects the liver. In PBC, the body’s immune system mistakenly attacks the small bile ducts within the liver, causing inflammation and gradual destruction of these ducts. Bile, a substance essential for digesting fats and removing toxins, becomes trapped in the liver, leading to liver damage over time.
“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,” said Joanne Quan, chief medical officer at Mirum, in a statement. “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.”
Read more about PBC treatment and care
The phase 2b VANTAGE study enrolled about 180 patients since 2021 and used the adult itch reported outcome questionnaire to compare improvements in pruritus perception between patients receiving volixibat and those who received a placebo.
Preliminary results found that patients receiving the drug experienced significant improvement in pruritus and fatigue compared to those on placebo. Laboratory workup revealed a 50% decrease in serum bile acids in 75% of patients, the company said. The drug appeared to be safe, with adverse effects being mild to moderate. Diarrhea was the most frequent adverse effect.
The expected completion date of the VANTAGE study is December 2025.
Pruritus is one of the most common complaints among patients with PBC and can significantly affect quality of life. The mechanisms behind PBC pruritus are not fully understood, but research suggests that bile acid accumulation could play a significant role.
Volixibat inhibits the ileal bile acid transporter. This receptor is responsible for the reuptake of bile acids in the small intestines; its inhibition leads to increased bile acid excretion through feces.
