Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic, progressive autoimmune liver disease. Because it is asymptomatic in its early stages, it is called the "silent liver disease." The patient's immune system mistakenly attacks the small bile ducts in the liver, causing bile stasis and continuous damage to liver cells, eventually potentially leading to cirrhosis and liver failure.
On March 19 , 2026, local time, GlaxoSmithKline (GSK) announced that the U.S. FDA has approved linerixibat for the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis (PBC) . According to a GSK press release, this is the first drug approved for this indication in the United States .
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Publicly available information shows that Linerixibat is an oral IBAT inhibitor with the potential to treat cholestatic pruritus associated with primary biliary cholangitis (PBC). By inhibiting bile acid reabsorption, Linerixibat reduces various pruritus mediators in circulation. The US FDA and the European Medicines Agency (EMA) have granted Linerixibat Orphan Drug Designation for the treatment of cholestatic pruritus associated with PBC. The New Drug Application (NDA) for this product was accepted by the FDA and EMA in June 2025, with the indication being the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis (PBC). On February 25, 2026 , the application for marketing authorization of Linerixibat tablets in China was accepted.
This approval is based on positive results from the Phase 3 clinical trial GLISTEN, in which linerixibat was previously administered. GLISTEN was a double-blind, randomized, placebo-controlled Phase 3 trial that enrolled 238 patients with pneumoconiotic cholestatic pruritus (PBC), who were initially randomized 1:1 to the active drug group and the placebo group. The primary analysis evaluated the efficacy and safety of linerixibat compared to placebo.
The GLISTEN trial met its primary endpoint, showing that patients treated with linerixibat (n=119) experienced significant improvement in pruritus over 24 weeks, compared to the placebo group (n=119). The least-squares mean difference between the two groups was -0.72, assessed using the Most Intense Pruritus Rating Scale-NRS. These results suggest that linerixibat holds promise for alleviating intractable pruritus, a major symptom in patients with pneumococcal erythema (PBC).
The study also achieved several key secondary endpoints, including improvement in pruritus scores at week 2 and improvement in pruritus-related sleep disturbance scores over 24 weeks. Specifically, pruritus improvement was rapid, showing superiority over the placebo group by week 2 , with a statistically significant difference, and the efficacy was maintained throughout the trial period. During the 24-week treatment period, linerixibat significantly improved pruritus-induced sleep disturbances compared to placebo, a symptom that significantly impacts patients' quality of life. By week 24, 56% of patients in the linerixibat group showed clinically significant improvement in pruritus scores (a reduction of ≥3 points in WI-NRS), compared to 43% in the placebo group, a difference of 13% between the treatment groups.
It's worth noting that on March 9, 2026, GSK announced a collaboration with Alfasigma. Under the agreement, Alfasigma will acquire exclusive global rights to develop, manufacture, and commercialize linerixibat .
Under the agreement, GSK will receive an upfront payment of $300 million , plus $100 million in milestone payments following FDA approval in the United States (expected before the transaction closes, PDUFA date is March 24, 2026). Additionally, approvals in the European Union and the United Kingdom will trigger $20 million in milestone payments, with sales-related milestone payments potentially reaching $270 million. GSK will also receive tiered double-digit percentage royalties based on global net sales.
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PBC, a cholestatic liver disease, obstructs the flow of bile in the liver. The resulting excess of circulating bile acids is considered a contributing factor to cholestatic pruritus (an endogenous pruritus that cannot be relieved by scratching). This pruritus can occur at any stage of PBC disease or in its biochemical control, varying in severity, and is present in approximately 90% of PBC patients. While first-line treatment for PBC can control the disease in about 70% of patients, it does not reduce the severity or impact of the pruritus. Cholestatic pruritus is a potentially disabling and serious condition, causing sleep disturbances, fatigue, decreased quality of life, and may even require a liver transplant in the absence of liver failure.
Currently, among the IBAT (ileal bile acid transporter) drugs used to treat cholestatic pruritus, there is also Maralixibat, developed by Mirum Pharmaceuticals. In September 2021, Maralixibat received FDA approval in the United States for the treatment of cholestatic pruritus in patients aged 1 year and older with ALGS. Maralixibat is also undergoing a global Phase 2b clinical trial (EMBARK) for the treatment of biliary atresia (BA).
The FDA approval of Linerixibat in the United States represents a significant milestone in the treatment of PBC (Potentially Infectious Disease) itching. It is hoped that GSK's Linerixibat tablets will be approved for marketing in China soon, providing more treatment options for patients.
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