Lynavoy (linerixibat): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat cholestatic pruritus associated with primary biliary cholangitisWording from FDA's list of novel approvals.
FDA review
Standard reviewOrphan drug
Company
Intercept
Application
NDA 220295
Specialty
Gastroenterology
At a glance
Lynavoy (linerixibat) is an ileal bile acid transporter inhibitor approved March 17, 2026 for cholestatic pruritus associated with primary biliary cholangitis in adults. In the phase 3 GLISTEN trial, itch improved more with linerixibat than placebo over 24 weeks (adjusted mean difference -0.72 points on the 0 to 10 Worst Itch scale; P=0.0013). Diarrhea was the main safety issue, and there is no boxed warning.
What it is and how it works
Linerixibat reversibly blocks the ileal bile acid transporter. This reduces bile acid reabsorption in the terminal ileum and increases bile acid loss in stool. Serum bile acids and other itch mediators fall, though the full mechanism of itch relief is unknown. It acts on the gut, unlike resins that bind bile acids in the gut lumen or drugs that act on opioid or other central pathways.
Phase 3, randomized, multicenter, double-blind, placebo-controlled, 24-week trial at 115 centers in 19 countries. Randomization was stratified by itch severity and concomitant itch treatment.
Patients
238 adults with PBC and moderate-to-severe pruritus (Worst Itch score of 4 or higher). Ages ranged from 30 to 80 years. Most (97%) took ursodiol at baseline, and 47% took other antipruritic drugs. About 10% in each arm had compensated cirrhosis.
Compared with
Matching placebo (119 patients) versus linerixibat at the approved dose twice daily (119 patients).
Primary endpoint
Change in pruritus over 24 weeks on the Worst Itch Numerical Rating Scale (0 = no itch, 10 = worst imaginable itch).
Result
Least-squares mean change from baseline was -2.86 (95% CI -3.23 to -2.50) with linerixibat and -2.15 (95% CI -2.51 to -1.78) with placebo. Adjusted mean difference was -0.72 (95% CI -1.15 to -0.28; P=0.0013).
Other results
Key secondary results are not given in the sources provided. A separate analysis of GLISTEN data proposed a reduction of at least 3 points on the Worst Itch scale as a meaningful within-patient improvement.
Safety in the trial
Diarrhea occurred in 61% with linerixibat versus 18% with placebo, and abdominal pain in 18% versus 3% in the publication. Discontinuation for GI events occurred in 7% versus under 1%. Serious adverse events occurred in 12% versus 3%. Discontinuation for any adverse reaction was 14% versus 5% per the label. Liver enzyme increases and bleeding events were more common with linerixibat. No deaths occurred.
How does Lynavoy (linerixibat) compare with the alternatives (Cholestyramine, Rifampin, Naltrexone) for cholestatic pruritus associated with primary biliary cholangitis? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
There is no boxed warning. Diarrhea is the most common adverse reaction and led to discontinuation in some patients. Patients should be advised to watch for dehydration. The label also warns of liver test elevations, fat-soluble vitamin deficiency, bleeding and fracture risk, which is a concern seen with IBAT inhibitors. Baseline liver tests, vitamin levels and INR should be checked and followed during treatment. Use should be avoided in decompensated cirrhosis or prior or active hepatic decompensation.
What it competes with
Cholestatic itch in PBC is treated in steps, usually alongside disease-directed therapy such as ursodiol. Options are mostly used off label for itch and are limited by tolerability.
CholestyramineBile acid binding resin often tried first for itch. Taste, GI effects and interference with other drugs limit use.
RifampinEnzyme inducer used for itch that does not respond to resins. Requires liver monitoring because of hepatotoxicity and has many drug interactions.
NaltrexoneOpioid antagonist used for refractory itch. It can cause opioid withdrawal-like symptoms and requires care in patients taking opioids.
SertralineSSRI used off label for cholestatic itch when other options fail. Evidence is limited.
Odevixibat or maralixibatOther IBAT inhibitors approved for cholestatic pruritus in other cholestatic liver diseases, not PBC.
Bottom line for clinicians
Lynavoy is for adults with PBC and cholestatic pruritus who do not have decompensated liver disease. The itch benefit over placebo was modest on the numeric scale, while diarrhea and abdominal pain were frequent and caused more discontinuations. Plan baseline and ongoing liver and vitamin monitoring, and discuss expected GI effects before starting.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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