CHMP Recommends EU Approval of Linerixibat for Cholestatic Pruritus in Primary Biliary Cholangitis
Key Insights
The EMA's CHMP has recommended EU approval of linerixibat for treating cholestatic pruritus (search) in adults with primary biliary cholangitis (search) (PBC), with a final European Commission decision expected in the coming months.
Cholestatic pruritus (search) affects up to 89% of PBC patients, causing severe quality-of-life impairment including sleep disturbance and chronic fatigue, with up to one-third of patients receiving no treatment.
The positive opinion is based on the Phase III GLISTEN trial, which met its primary and key secondary endpoints, demonstrating rapid, significant, and sustained improvement in pruritus and sleep interference versus placebo.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of linerixibat in the European Union for the treatment of cholestatic pruritus (search) in adult patients with primary biliary cholangitis (search) (PBC). The final decision from the European Commission is anticipated in the coming months.
The recommendation marks a significant regulatory milestone for a patient population that has long lacked dedicated therapeutic options for one of the most distressing symptoms of PBC. Linerixibat is already approved in the United States and the United Kingdom. Alfasigma (search) holds exclusive global rights to develop, manufacture, and commercialize linerixibat following a licensing agreement with GSK plc.
The Burden of Cholestatic Pruritus (search) in PBC
Primary biliary cholangitis (search) is a rare autoimmune liver disease that can progress to cirrhosis, liver failure, and the need for liver transplantation. Cholestatic pruritus (search)—a sensation of internal itching that cannot be relieved by scratching—affects up to 89% of people with PBC. The symptom can manifest at any stage of the disease and independently of biochemical disease control.
The impact on quality of life is profound. Patients experience sleep disturbances, chronic fatigue, and diminished overall well-being. In severe cases, patients may require liver transplantation even in the absence of liver failure. Data from the United States indicate that pruritus is frequently undocumented in medical records, and up to one-third of patients with clinically significant pruritus receive no treatment at all.
In PBC, a cholestatic liver disease, bile flow from the liver is impaired. The resulting excess of circulating bile acids triggers cholestatic pruritus (search). Linerixibat is an ileal bile acid transporter (IBAT (search)) inhibitor that reduces circulating levels of multiple pruritus mediators.
Phase III GLISTEN Trial Results
The CHMP's positive opinion is grounded in the results of the Phase III GLISTEN study. The trial met its primary endpoint and key secondary endpoints, demonstrating a rapid, significant, and sustained improvement in cholestatic pruritus (search) and in the interference of pruritus on sleep compared with placebo. The safety profile of linerixibat was consistent with findings from previous studies and with the mechanism of IBAT (search) inhibition.
Industry Perspective
Francesco Balestrieri, CEO of Alfasigma (search), characterized the CHMP recommendation as a fundamental milestone for people with PBC who suffer from cholestatic pruritus (search). "This recommendation brings us closer to the goal of making a new therapeutic option available for eligible patients—subject to regulatory approval and local access pathways—and supports Alfasigma's strategy to consolidate its business in specialty care and rare diseases, addressing complex health challenges in gastroenterology and immunology," Balestrieri stated.
The European Commission's final decision is expected in the coming months. If granted marketing authorization, linerixibat would become the first approved therapy in the EU specifically indicated for cholestatic pruritus (search) in PBC, addressing a significant unmet medical need for a patient population that has historically been undertreated.