FDA Approves Linerixibat for Cholestatic Pruritus in Primary Biliary Cholangitis

The FDA has approved linerixibat (Lynavoy; GSK), marking a significant milestone in the management of primary biliary cholangitis (PBC). Linerixibat is the first medicine approved in the US specifically for the treatment of cholestatic pruritus in adult patients with PBC, addressing a condition that has long lacked dedicated pharmacologic options.¹

Understanding PBC

PBC is a rare autoimmune cholestatic liver disease in which bile flow from the liver is progressively disrupted. The resulting accumulation of bile acids in circulation is thought to play a causal role in cholestatic pruritus—an internal itch that cannot be relieved by scratching.^1,2 The symptom is far more prevalent than is often recognized, affecting up to 90% of people living with PBC.² Its consequences extend well beyond physical discomfort: patients commonly experience sleep disturbance, debilitating fatigue, and significantly impaired quality of life.^1,2 Pruritus can occur at any stage of PBC disease or biochemical control, and the condition's burden can be so profound that some patients require liver transplantation even in the absence of end-stage liver failure. Despite this impact, effective approved treatment options have historically been limited, and the first-line treatment for PBC that controls the underlying disease does not reduce the severity or impact of pruritus.¹

Mechanism of Action

Linerixibat is an ileal bile acid transporter (IBAT) inhibitor—a targeted, oral agent designed to interrupt the enterohepatic recirculation of bile acids. By inhibiting bile acid re-uptake in the ileum, linerixibat reduces multiple circulating mediators implicated in pruritus.^1,2 This mechanism directly targets the underlying bile acid dysregulation driving cholestatic itch, representing a mechanistically distinct approach compared to previously used off-label options.

Clinical Evidence: The GLISTEN Trial

The FDA approval is based on data from the global GLISTEN (NCT04950127) phase 3 trial, a double-blind, randomized, placebo-controlled study conducted across 19 countries that met both its primary and key secondary end points.^1,2,3 The trial demonstrated significant, rapid, and sustained improvements in cholestatic pruritus and itch-related sleep interference versus placebo, with meaningful reductions observed as early as week 2 and maintained throughout 24 weeks of treatment.²

The primary end point assessed change from baseline in monthly itch score using a 0–10 numerical rating scale (NRS) for worst itch (WI-NRS). Linerixibat (n=119) significantly outperformed placebo (n=119), with a least squares mean difference of -0.72 (95% CI: -1.15, -0.28; p=0.001). The key secondary end point of itch-related sleep interference also reached statistical significance (LS mean difference: -0.53; 95% CI: -0.98, -0.07; p=0.024). Additionally, 56% of patients in the linerixibat group achieved a clinically meaningful reduction in itch (WI-NRS ≥3-point reduction) versus 43% in the placebo group at week 24.²

Safety Profile

The safety profile of linerixibat was consistent with its IBAT inhibition mechanism and findings from prior studies.^1,2 The most frequently reported adverse events were diarrhea (61%) and abdominal pain (18%), both predominantly mild to moderate in severity. Treatment discontinuation due to diarrhea occurred in 4% of patients receiving linerixibat versus less than 1% in the placebo group.^1,2 Pharmacists should proactively counsel patients on these gastrointestinal effects at treatment initiation to set appropriate expectations and support adherence.

Regulatory Context and Outlook

Linerixibat has received orphan drug designation in the US, EU, and Japan, and priority review in China, with marketing applications currently under regulatory review in the EU, UK, Canada, and China.¹ GSK has also entered a licensing agreement with Alfasigma S.p.A. for worldwide commercialization rights, pending applicable regulatory clearances. For pharmacists, this approval introduces the first targeted oral therapy for a condition with substantial unmet need—a meaningful addition to the PBC treatment landscape.

REFERENCES

1. Lynavoy (linerixibat) approved by the US FDA for cholestatic pruritus in patients with primary biliary cholangitis (PBC). GSK. Published March 19, 2026. Accessed March 19, 2026. https://www.gsk.com/en-gb/media/press-releases/lynavoy-linerixibat-approved-by-the-us-fda/

2. GLISTEN phase III trial results show linerixibat significantly improves cholestatic pruritus (relentless itch) in primary biliary cholangitis (PBC). GSK. Published May 8, 2025. Accessed March 19, 2026. https://www.gsk.com/en-gb/media/press-releases/glisten-phase-iii-trial-results-show-linerixibat-significantly-improves-cholestatic-pruritus/

3. Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN). Updated July 22, 2025. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT04950127