Linerixibat

GSK’s linerixibat helped reduce itch in patients with an autoimmune liver disease that affects the bile ducts, meeting its primary endpoint in a late-stage trial. If approved, linerixibat would be the first drug on the US market to treat itch related to primary biliary cholangitis, a condition that mainly affects women and can cause liver damage. It’s also associated with a relentless itch that feels like it’s under the skin. While first-line primary biliary cholangitis treatment may control the disease, it may not reduce the severity of itching, also known as pruritus. “Patients describe it as bugs crawling, and they want to dig it out,” Megan McLaughlin, GSK’s medicine development leader for linerixibat, told Endpoints News. Linerixibat helped reduce patients’ monthly itch score over 24 weeks compared to placebo in the Phase 3 GLISTEN trial, GSK announced Tuesday at the American Association for the Study of Liver Diseases conference. GSK didn’t have any hard data to share, as the trial remains ongoing. But the latest readout gives the company “all the data we need for the primary analysis, which is what we’ve agreed with global regulators to submit,” McLaughlin said. The company is planning regulatory submissions in the US and EU in the first half of 2025. Linerixibat is an ileal bile acid transporter (IBAT). It works by inhibiting the reuptake of bile acids, which is thought to be a root cause of itch in PBC patients. GSK estimates that 510,000 patients globally will have PBC by 2030, and just under half of those patients will experience a severe enough itch to require specific treatment. The drug could compete with Mirum’s rival IBAT inhibitor volixibat, which read out positive Phase 2b data in PBC in June. McLaughlin said linerixibat could have an advantage by getting to market first. “The itch associated with PBC for many patients is unrelenting and often severe but is a symptom that is frequently overlooked or dismissed,” Carol Roberts, president of a patient support group called The PBCers Organization, said in GSK’s news release. “It has a significant impact on quality of life and mental health for people with PBC.” Editor’s Note: This story has been updated to clarify the definition of PBC, and that there is one first-line option for PBC patients.

A Phase III study of GSK's linerixibat in adults with cholestatic pruritus associated with primary biliary cholangitis (PBC) met its primary endpoint, with top-line results showing that the oral drug significantly improved itch. "Linerixibat has the potential to be the first global therapy specifically developed to treat itch in PBC," noted Kaivan Khavandi, global head of respiratory/immunology R&D.The ongoing GLISTEN trial is investigating linerixibat — an ileal bile acid transporter (IBAT) inhibitor also known as GSK2330672 — in PBC patients with moderate-to-severe itch who were receiving stable doses of guideline-suggested therapies for pruritus, or were treatment naïve, or had been previously treated. Primary and secondary outcome measures were assessed using the Numerical Rating Scale (NRS) for worst itch and itch-related sleep interference, and the PBC-40 questionnaire for quality of life.Top-line results showed that linerixibat demonstrated a statistically significant reduction from baseline in monthly itch score over 24 weeks versus placebo. Further analysis is ongoing, with full data set to be presented at a future medical meeting.