Berlin, Germany – March 19, 2026 – In a significant advancement for patients battling the debilitating itch associated with primary biliary cholangitis (PBC), the U.S. Food and Drug Administration (FDA) has approved linerixibat for the treatment of cholestatic pruritus in adults. The approval, announced today by Alfasigma, marks the first targeted therapy specifically developed to address this challenging symptom of the rare autoimmune liver disease. This decision follows a positive Phase III trial and a New Drug Application (NDA) accepted for review in June 2025.
PBC, a chronic disease that slowly damages the bile ducts in the liver, often manifests with intense itching – cholestatic pruritus – that significantly impacts quality of life, disrupting sleep and daily activities. Current treatment options are limited and often provide inadequate relief. Linerixibat, an investigational targeted inhibitor of the ileal bile acid transporter (IBAT), offers a new approach by addressing the underlying mechanisms contributing to the itch.
Understanding Linerixibat and its Mechanism of Action
Linerixibat works by blocking the IBAT, a protein responsible for reabsorbing bile acids in the intestine. By inhibiting this process, linerixibat reduces the levels of bile acids that can accumulate and contribute to the sensation of itch in patients with cholestatic liver diseases like PBC. GSK, the original developer of linerixibat, highlighted the potential of the drug to “craft a difference in the lives of patients living with relentless itch associated with PBC and its related sleep interference.”
The FDA’s decision is based on data from the GLISTEN Phase III clinical trial, presented in May 2025 at the European Association for the Study of the Liver (EASL) Congress. The trial involved 238 patients with PBC and demonstrated that linerixibat led to both rapid and sustained improvements in cholestatic pruritus and itch-related sleep interference compared to a placebo. The safety profile observed in the GLISTEN trial was consistent with previous studies of IBAT inhibition.
A Collaborative Effort: GSK and Alfasigma
While GSK initially developed linerixibat and submitted the NDA to the FDA, the commercial future of the drug lies with Alfasigma. On March 9, 2026, just ten days prior to the FDA approval, GSK and Alfasigma announced a licensing agreement granting Alfasigma exclusive global rights to develop, produce, and commercialize linerixibat. Il Sole 24 Ore Radiocor reported that Francesco Balestrieri, CEO of Alfasigma, described the approval as “an important milestone for patients who will have access to the first treatment developed specifically for this rare and debilitating condition.”
Alfasigma brings significant experience in the development and commercialization of therapies for severe liver diseases, including PBC, and a strong global presence to the table. This partnership is expected to facilitate the widespread availability of linerixibat to patients in need worldwide.
The GLISTEN Trial: Key Findings
The GLISTEN trial was a double-blind, randomized, placebo-controlled study designed to evaluate the efficacy and safety of linerixibat in patients with PBC experiencing cholestatic pruritus. Patients were randomly assigned to receive either linerixibat or a placebo for an initial 24-week treatment period, with the possibility of continuing into a further study phase. The trial’s success hinged on demonstrating improvements in both the intensity of the itch and its impact on sleep. The positive results from GLISTEN were a critical component of the NDA submitted to the FDA.
What Does This Approval Imply for PBC Patients?
For the estimated 250,000 people in the United States living with PBC, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the approval of linerixibat represents a significant step forward. Currently, treatment options for PBC-related pruritus are largely palliative, focusing on symptom management rather than addressing the underlying cause. These include medications like cholestyramine, ursodeoxycholic acid, and antihistamines, which often provide limited relief and can have undesirable side effects.
Linerixibat offers a novel mechanism of action, targeting the root of the itch by modulating bile acid levels. This targeted approach has the potential to provide more effective and sustained relief for patients struggling with this debilitating symptom. Yet, it’s important to note that linerixibat is not a cure for PBC; it specifically addresses the pruritus associated with the disease.
Prescription Drug User Fee Act (PDUFA) Date
The FDA initially assigned a Prescription Drug User Fee Act (PDUFA) goal date of March 24, 2026, for its decision on the linerixibat NDA. The agency ultimately approved the drug prior to this date, demonstrating the priority given to addressing this unmet medical need. The PDUFA program, established by Congress, sets timelines for FDA review of new drug applications.
Looking Ahead: Availability and Future Research
With FDA approval secured, Alfasigma will now focus on making linerixibat available to patients. The company has not yet announced a specific launch date or pricing information. Further research may likewise be conducted to explore the potential of linerixibat in other cholestatic liver diseases and to optimize its leverage in combination with other therapies.
The approval of linerixibat underscores the importance of continued innovation in the treatment of rare diseases like PBC. By addressing the debilitating symptom of pruritus, this new therapy has the potential to significantly improve the quality of life for countless patients.
The next step will be monitoring the drug’s performance in real-world settings and gathering further data on its long-term safety and efficacy. Alfasigma will likely be working closely with healthcare professionals to ensure appropriate patient selection and management.
Do you have experience with PBC or know someone who does? Share your thoughts and questions in the comments below. And please share this article with anyone who might benefit from this important news.