The US FDA has approved Lynavoy (linerixibat) for the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis, GSK announced on March 19, 2026. Lynavoy is an ileal bile acid transporter (IBAT) inhibitor and the first medicine approved in the US for this indication. The approval also represents the first liver disease therapy to emerge from GSK's pipeline. GSK previously announced a licence agreement under which Alfasigma S.p.A. will acquire worldwide rights to develop, manufacture, and commercialise linerixibat, a transaction that remains subject to regulatory clearances.
Lynavoy has been granted Orphan Drug Designation in the US, EU, and Japan, and priority review in China. Marketing applications are ongoing in the EU, UK, Canada, and China. The approved indication covers adult patients with PBC who experience cholestatic pruritus, an internal itch driven by excess circulating bile acids that cannot be relieved by scratching. Up to 89% of people living with PBC experience this symptom, which can cause sleep disturbance, fatigue, and reduced quality of life. In some cases, the severity of pruritus has led to liver transplantation even in the absence of liver failure.
The approval was based on the GLISTEN Phase III trial, a double-blind, randomised, placebo-controlled study enrolling 238 patients. The trial met both its primary and key secondary endpoints. The primary endpoint, change from baseline in monthly worst-itch numerical rating scale score over 24 weeks, showed linerixibat (n=119) produced a least squares mean difference of -0.72 (95% CI: -1.15, -0.28; p=0.001) versus placebo (n=119). Itch improvement was observed as early as week two (p≤0.001), and itch-related sleep interference also improved over 24 weeks (p=0.024). The most frequently reported adverse events were diarrhoea (61%) and abdominal pain (18%), both mostly mild to moderate. Treatment discontinuation due to diarrhoea occurred in 4% of linerixibat-treated patients versus less than 1% on placebo, and discontinuation due to abdominal pain occurred in 4% versus none on placebo. The safety profile was consistent with the known mechanism of IBAT inhibition.
Prior to this approval, no therapy carried a US FDA indication for cholestatic pruritus in PBC. Management relied on off-label use of cholestyramine, rifampicin, naltrexone, and sertraline in a stepwise approach, with variable efficacy and tolerability. Linerixibat works by inhibiting bile acid reuptake in the ileum, reducing multiple circulating mediators of pruritus. The approval validates IBAT inhibition as a therapeutic strategy in this setting and adds to a growing field of agents targeting bile acid transport. Volixibat, developed by Mirum Pharmaceuticals, received FDA Breakthrough Therapy Designation in late 2024 for the same indication and is in Phase III development. Odevixibat (Bylvay), marketed by Ipsen, is approved for cholestatic pruritus in pediatric cholestatic diseases but not in PBC. Beyond bile acid modulators, mechanistically distinct candidates including nalbuphine ER (Trevi Therapeutics), targeting opioid receptor pathways, and EP547 (Escient Pharmaceuticals), an MRGPRX4 antagonist, are also in clinical development for PBC-associated pruritus. The breadth of this pipeline reflects the recognition that cholestatic pruritus remains inadequately controlled for many patients despite the availability of a first approved option.
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