Drug Update · Gastroenterology

FDA Approves Linerixibat for PBC Pruritus: -0.72 WI-NRS in GLISTEN

July 11, 2026

Approval date

03/17/2026

Indication

treatment of cholestatic pruritus associated with primary biliary cholangitis (PBC) in adult patients

Primary endpoint result

Adjusted mean difference in WI-NRS -0.72 (95% CI -1.15 to -0.28); p=0.0013

Trial

GLISTEN (randomised, multicentre, double-blind, placebo-controlled, phase 3)

Dose (label)

40 mg orally twice daily

Clinical Perspective

This approval affects hepatologists, gastroenterologists, and clinicians treating adults with PBC-associated cholestatic pruritus by adding linerixibat (Lynavoy) as an FDA‑approved oral option for symptomatic itch in this population ^[2]^[3]. The GLISTEN data support a modest but statistically significant reduction in WI-NRS versus placebo over 24 weeks, with a tradeoff of increased diarrhoea and other gastrointestinal events that may require interruption or discontinuation ^[1]^[3]. What remains to be defined for practice is the optimal monitoring schedule for liver tests and fat‑soluble vitamin levels during longer-term LYNAVOY therapy?

Dr. Sanjay Iyer · Gastroenterology

The FDA approved linerixibat (Lynavoy) for the treatment of cholestatic pruritus associated with primary biliary cholangitis (PBC) in adult patients on 03/17/2026 based on the GLISTEN trial, which showed an adjusted mean difference in Worst Itch Numerical Rating Scale (WI-NRS) of -0.72 versus placebo over 24 weeks ^[2]^[1]. The approval and label incorporate randomized phase 3 efficacy data and safety findings from the GLISTEN study ^[2]^[1].

Clinical Context

Linerixibat is an ileal bile acid transporter (IBAT) inhibitor developed for cholestatic pruritus in PBC and marketed under the trade name Lynavoy by Intercept Pharmaceuticals, Inc. (a wholly owned subsidiary of Alfasigma S.p.A.), the sponsor listed on the FDA approval record ^[2]. The drug’s mechanism is inhibition of the ileal bile acid transporter, decreasing reabsorption of bile acids in the terminal ileum and increasing fecal elimination; reduction of serum bile acids and other pruritogenic mediators is cited as a putative pathway for itch reduction ^[4]^[3]. Cholestatic pruritus is described in the trial background as common and undertreated in PBC ^[1].

Key Findings

The GLISTEN trial (randomised, multicentre, double-blind, placebo-controlled, phase 3) showed that linerixibat reduced pruritus as measured by the WI-NRS over 24 weeks: least-squares mean change from baseline -2.86 for linerixibat versus -2.15 for placebo, with an adjusted mean difference -0.72 (95% CI -1.15 to -0.28); p=0.0013 ^[1].
A secondary efficacy measure, pruritus-related sleep interference, improved with linerixibat versus placebo: least-squares mean difference -0.53 (95% CI -0.98 to -0.07); p=0.024 over 24 weeks ^[4].
The trial enrolled 238 patients randomized 1:1 (119 linerixibat, 119 placebo) with baseline Monthly Itch Score mean ~7.3 and mean Monthly Sleep Score ~6.3 ^[1]^[4].

Safety & Tolerability

Diarrhoea: 72 (61%) of 119 patients treated with linerixibat had diarrhoea versus 21 (18%) of 118 for placebo in GLISTEN; most events occurred early in treatment ^[1].
Abdominal pain: 22 (18%) with linerixibat versus four (3%) with placebo in GLISTEN ^[1].
Nausea: reported among common adverse reactions in the labeling and occurred in the trial population (10% linerixibat vs 9% placebo reported in labeling summary) ^[3]^[4].
Increased alanine aminotransferase (ALT): listed as a common adverse reaction in the label and observed as liver test elevations in the trial population ^[3]^[1].
Increased aspartate aminotransferase (AST): listed as a common adverse reaction in labeling ^[3].
Hemorrhage: hemorrhagic events were listed among common adverse reactions in the label ^[3].
Serious adverse events: reported in 14 (12%) of 119 patients receiving linerixibat versus four (3%) of 118 receiving placebo in GLISTEN ^[1].
Treatment discontinuations due to gastrointestinal adverse events: eight (7%) of 119 in the linerixibat group (five due to diarrhoea) versus one (<1%) of 118 in the placebo group in GLISTEN ^[1].
No deaths were reported during the GLISTEN study ^[1].
Fat-soluble vitamin deficiency: the approved label warns that linerixibat may adversely affect absorption of fat-soluble vitamins and recommends baseline and periodic monitoring with supplementation as needed ^[3].
Fracture risk: labeling notes that IBAT inhibitors have been associated with bone fractures and recommends monitoring bone health and ensuring adequate fat-soluble vitamin levels ^[3].

Study Design

GLISTEN was a randomized, multicentre, double-blind, placebo-controlled, phase 3 trial (ClinicalTrials.gov NCT04950127) that enrolled 238 patients with PBC and moderate-to-severe pruritus (WI-NRS ≥4); patients were randomized 119 to linerixibat 40 mg twice daily and 119 to placebo and treated for 24 weeks with primary endpoint change in WI-NRS ^[1]^[4]. Clinicians should consult current prescribing information for full dosing guidance. The FDA granted marketing approval for Lynavoy on 03/17/2026 for the treatment of cholestatic pruritus associated with PBC in adults; Lynavoy has orphan designation for PBC and labeling includes safety monitoring guidance ^[2]^[3].

FAQ

What is linerixibat (Lynavoy) approved for?

Lynavoy (linerixibat) is approved for the treatment of cholestatic pruritus associated with primary biliary cholangitis (PBC) in adult patients. The approval follows a phase 3 randomized trial (GLISTEN) demonstrating improvement in patient-reported itch over 24 weeks. The indication and limitations, including avoidance in patients with decompensated cirrhosis, are described in the prescribing information.

How does linerixibat work?

Linerixibat is an ileal bile acid transporter (IBAT) inhibitor that decreases reabsorption of bile acids in the terminal ileum, increasing fecal bile acid elimination. The label and clinical data note that inhibition of IBAT reduces mediators associated with pruritus, including serum bile acids, and this mechanism is the basis for its antipruritic effect in PBC.

What is the recommended dose of linerixibat (Lynavoy)?

The recommended dose in the label is 40 mg taken orally twice daily, with tablets swallowed whole at least 30 minutes before any food or beverage other than water. If taken with bile acid binding resins, the label advises administering linerixibat at least 4 hours before or 4 hours after the resin. Clinicians should consult current prescribing information for complete dosing guidance.

What are the most common side effects of linerixibat?

Across the GLISTEN trial and the approved label, the most commonly reported adverse reactions include diarrhoea, abdominal pain, nausea, increased ALT, hemorrhage, increased AST, headache, dyspepsia, gastroesophageal reflux disease, abdominal distension, dizziness, and arthralgia. Diarrhoea and abdominal pain were markedly more frequent with linerixibat than placebo in GLISTEN; diarrhea onset was often early in treatment and led to some discontinuations. The label also warns about liver test elevations, fat‑soluble vitamin deficiency, and an association of IBAT inhibitors with bone fractures; monitoring guidance and supplementation recommendations are provided in the prescribing information.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Linerixibat for PBC Pruritus: -0.72 WI-NRS in GLISTEN

Direct Clinical Takeaway & Evidence Summary

FDA Approves Linerixibat for PBC Pruritus: -0.72 WI-NRS in GLISTEN

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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