FDA Approves First Drug for Cholestatic Pruritus in Primary Biliary Cholangitis

The U.S. Food and Drug Administration has approved linerixibat, marking the first treatment specifically indicated for cholestatic pruritus in patients with Primary Biliary Cholangitis. The announcement was made by GlaxoSmithKline, highlighting a significant advancement in managing this distressing symptom associated with PBC.

GSK previously announced on 9 March a licence agreement under which Alfasigma S.p.A. will acquire worldwide exclusive rights to develop, manufacture and commercialise linerixibat. This transaction is ongoing and is subject to customary conditions, including applicable regulatory agency clearances such as under the Hart-Scott-Rodino Act in the US.

Cholestatic pruritus is an internal itch experienced by up to 89% of people living with PBC, a rare autoimmune disease that can lead to liver failure. It is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life and even sometimes requiring liver transplantation in the absence of liver failure.

Kaivan Khavandi, SVP, R&D Head Respiratory, Immunology & Inflammation, and Head of GSK Translational & Development Sciences, GSK, said: “The approval of Lynavoy in the US gives patients a much needed treatment option that offers rapid, significant and sustained improvement in the debilitating effects of itch caused by PBC. For many patients, cholestatic pruritus remains a persistent, poorly addressed condition. This is the first liver medicine from our pipeline to receive approval, underscoring our commitment to developing meaningful innovation across the spectrum of liver disease.”

Christopher Bowlus M.D., Lena Valente Professor and Chief of Gastroenterology and Hepatology, University of California Davis, said: “The approval of linerixibat represents an important opportunity to improve the lives of people with PBC and who struggle with uncontrolled and often debilitating pruritus. The impact of itch on people living with PBC can be profound and treatment options have until now been limited. The FDA’s decision marks a major milestone in PBC pruritus care that addresses a critical area of unmet need.”

Carol Roberts, President, The PBCers Organization, said: “Cholestatic pruritus has been underestimated and overlooked for far too long, despite its significant impact on people living with PBC. Seeing a treatment specifically developed for chronic itch finally reach patients is a significant step forward and offers hope for those in need.”

The approval is based on data from the global GLISTEN phase III trial which met both primary and key secondary endpoints, demonstrating significant, rapid (at week two) and sustained (over 24 weeks) improvements in cholestatic pruritus and itch-related sleep interference versus placebo.

Linerixibat has been granted Orphan Drug Designation in the US, EU and Japan, and priority review in China, for the treatment of cholestatic pruritus in patients with PBC. Marketing applications for linerixibat are ongoing in the EU, UK, Canada and China.

About cholestatic pruritus in PBC

In PBC, a rare cholestatic liver disease, bile flow from the liver is disrupted. The resulting excess bile acids in circulation are thought to play a causal role in cholestatic pruritus, an internal itch that cannot be relieved by scratching. Pruritus can occur at any stage of PBC disease or biochemical control. It is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life and even sometimes requiring liver transplantation in the absence of liver failure.

About Lynavoy (linerixibat)

Linerixibat is an IBAT inhibitor, a targeted oral agent to treat cholestatic pruritus (itch) associated with the rare autoimmune liver disease PBC.8 By inhibiting bile acid re-uptake, linerixibat reduces multiple mediators of pruritus in circulation.

About the GLISTEN trial

GLISTEN is a double-blind, randomised, placebo-controlled, phase III trial. The primary and key secondary endpoints of the study were met, demonstrating significant, rapid (at week two), and sustained (over 24 weeks) improvements in cholestatic pruritus (p<=0.001) and itch-related sleep interference (p=0.024) versus placebo. The primary endpoint of change from baseline in monthly itch score showed linerixibat (n=119) significantly improved itch versus placebo (n=119) over 24-weeks, as measured on a 0-10 numerical rating scale (NRS) for the worst itch (WI-NRS) (least squares [LS] mean difference [95% CI]: -0.72 [-1.15, -0.28], p=0.001). The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition. The most frequently reported adverse events were diarrhoea (61%) and abdominal pain (18%), both of which were mostly mild to moderate. Treatment discontinuation due to diarrhoea was in 4% of patients versus <1% in placebo, and abdominal pain in 4% versus none in placebo.