New Pill for Itch from a Bile-Duct Disease

Lynavoy (linerixibat; pronounced LIN-ah-voy) is an oral ileal bile acid transporter (IBAT) inhibitor. It is a purple 40 mg film-coated tablet. It is not a topical cream. It is not ursodeoxycholic acid (UDCA), obeticholic acid, elafibranor, or seladelpar. It is labelled for cholestatic itch in adults with primary biliary cholangitis, not as a disease-modifying PBC therapy on the US indication sentence.

The FDA approved it on 17 March 2026 (NDA 220295). The UK MHRA authorised it on 1 May 2026. Europe’s medicines committee gave a positive opinion on 23 July 2026; that is not a European Commission marketing authorisation yet. Canada’s drug regulator has the file on the Submissions Under Review list (accepted August 2025) — under review, not a Notice of Compliance, and not a refusal.

US commercial labelling is now under Intercept Pharmaceuticals, Inc. (an Alfasigma company), with the Lynavoy trademark licensed from GSK. Development and the pivotal trial were GSK’s.

This is not a cure for PBC. It is a labelled option for the itch that can dominate sleep and daily life.

Where this is taking place

The pivotal 24-week readout is done. GLISTEN is COMPLETED. Long-term safety follow-up (LLSAT) remains ACTIVE_NOT_RECRUITING. Neither is a walk-in enrolment slot for a first commercial script in the United States or United Kingdom.

GLISTEN — NCT04950127 (GSK 212620) — Phase 3, randomised, double-blind, placebo-controlled, two-part study of linerixibat for cholestatic pruritus in PBC. Actual n=238. Status COMPLETED (CT.gov last update 22 Jul 2026). Start 27 Aug 2021. Primary completion 28 Oct 2024. Completion 20 Dec 2024. Sponsor: GlaxoSmithKline. Overall official on CT.gov: GSK Clinical Trials (study director) — no named site PI. Company materials describe 19 countries including the Americas, Europe, China, and Japan. Live CT.gov no longer lists Canadian GLISTEN sites after completion. Historical site mirrors list Canadian GSK Investigational Site addresses in Edmonton, Alberta (T6G 2X8), Ottawa, Ontario (K1H 8L6), and Toronto, Ontario (M5G 2C4). Those are historical mirrors only, not open enrolment and not a Canadian DIN.

LLSAT — NCT04167358 (GSK 212358) — Long-term safety and tolerability in PBC cholestatic pruritus. Status ACTIVE_NOT_RECRUITING. Actual n=242. Estimated completion 30 Sep 2026. This is the trial named in the FDA PMR for liver injury, bone health, and bleeding. Canadian CT.gov sites: Edmonton and Toronto (same GSK Investigational Site pattern). Not a commercial first-script door.

Commercial supply (labelled): United States (DailyMed marketing start 11 Jun 2026). United Kingdom (MHRA authorised; NHS funding not settled). European Union: wait for an EC decision after CHMP. Canada: SUR only.

Approval matrix

Access by country

• United States: Hepatology / gastroenterology clinician experienced in PBC. FDA-labelled 17 Mar 2026 for adults with cholestatic pruritus associated with PBC. One 40 mg tablet by mouth twice daily (morning and evening). Swallow whole with water. Take at least 30 minutes before any food or drink except water. If you use a bile acid–binding resin (cholestyramine, colesevelam), separate by at least 4 hours. DailyMed marketing start 11 Jun 2026 (Intercept / Alfasigma pack, NDC 69516-140-60). Baseline and ongoing liver tests and fat-soluble vitamin / INR monitoring are on the label. Avoid if you have decompensated cirrhosis or prior/active decompensation events. Intercept AE / pregnancy exposure line on the current USPI: 1-844-782-4278; www.lynavoy.com; FDA MedWatch 1-800-FDA-1088. No copay dollars here. Prior authorization still applies. Children not established.

• United Kingdom: MHRA authorised 1 May 2026 for itch in adults with PBC. Oral tablet twice daily per GOV.UK. Prescription-only. NICE GID-TA11307 is awaiting development — not a yes for routine NHS funding. Ask the liver clinic that already manages your PBC; do not assume NHS entitlement from the licence alone. Yellow Card for suspected side effects. Follow the clinic’s published SmPC when available.

• Canada (zoom): No retrieved NOC or DIN. Health Canada SUR lists linerixibat (accepted 2025-08, GSK Inc., new active substance). That is under review, not a refusal, and not Health Canada/FDA Approved. Provincial / territorial / NIHB / RAMQ listing is N/A until NOC. GLISTEN/LLSAT Canadian sites are historical / follow-up, not a commercial bottle. SAP for a non-marketed drug is unknown. Do not mail-order a US bottle as the plan.

• European Union: CHMP positive opinion 23 Jul 2026. No Commission marketing authorisation retrieved. A CHMP opinion is not an EU pack. DIY-import is not a plan. Named-patient import is a specialist/legal plan only where local law allows.

• China / Japan / Australia / Switzerland / elsewhere: Independent licence not retrieved on documents checked. Specialist + local special-access / trial only if those programs apply. No retrieved expanded-access or compassionate-use programme on the sources checked.

If your regulator has not authorised it: do not import on your own.

Who is eligible (from the labels)

United States (USPI / DailyMed):

• Adult with cholestatic pruritus associated with PBC.
• 40 mg orally twice daily; swallow whole; ≥30 minutes before food/beverage other than water.
• Avoid if decompensated cirrhosis or prior/active hepatic decompensation (variceal bleed, ascites, hepatic encephalopathy).
• Mild hepatic impairment (Child-Pugh A): same dose. Moderate/severe decompensated disease: not evaluated — avoid.
• Pediatrics: safety and efficacy not established.
• Contraindications: None listed.
• Separate from bile acid–binding resins by ≥4 hours.

United Kingdom (MHRA GOV.UK summary; SmPC pending retrieval):

• Adults with PBC itch; oral film-coated tablet; one tablet twice a day.
• Follow the published SmPC when the clinic has it for any further UK-specific detail.

Canada: No Product Monograph yet. Eligibility for a Canadian script does not exist until a NOC/DIN.

Not the labelled US conversation:

• Using it as a stand-alone disease-modifying PBC drug (the US indication is pruritus).
• Decompensated cirrhosis / decompensation history.
• Children.
• Topical use (there is no topical Lynavoy).

What the pivotal study showed (label vs journal)

Use the label of the country that will prescribe.

GLISTEN (Study 1, USPI §14 / NCT04950127): 238 adults with PBC and pruritus; Monthly Itch Score ≥4 at entry; randomised to linerixibat 40 mg BID or placebo for 24 weeks. Mean age 55.8; 95% female; 97% on UDCA; 47% on other antipruritics.

Week-2 weekly itch already favoured Lynavoy (LS mean difference −0.71; p<0.001).

CHMP opinion text cites Monthly Itch Score LS mean difference −0.68 (−1.14 to −0.23); p=0.003 — same trial family as the USPI −0.72 figure, with different rounding/model presentation. Use the label of the country that will prescribe.

Journal (not the label): Hirschfield GM et al. Lancet Gastroenterol Hepatol. 2026;11:22–33. DOI 10.1016/S2468-1253(25)00192-X. Peer-reviewed. Use the label for prescribing.

This is an itch and sleep-interference benefit versus placebo, not a survival trial and not a substitute for UDCA or other disease-directed PBC care.

How it is taken (labelled US)

• 40 mg tablet twice daily (morning and evening).
• Swallow whole with water.
• Take at least 30 minutes before any food or beverage other than water (so the drug reaches the gut before bile acids are released with eating).
• Missed dose: take as soon as possible and ≥30 minutes before the next meal; if more than 6 hours late, skip; do not double.
• Bile acid–binding resins: take Lynavoy ≥4 hours before or ≥4 hours after.
• Store 20–25°C in the original bottle with the desiccant; keep closed; do not swallow the desiccant canister.
• Bottle of 60 tablets = about one month at twice-daily dosing (NDC 69516-140-60).

Safety (from the USPI; FDA also required long-term PMR work)

Warnings and Precautions:

• Liver test elevations — more common than placebo (14% vs 6% any elevation signal in Study 1). Get baseline ALT, AST, total and direct bilirubin, ALP; monitor as for PBC care; intensify monitoring if new elevations; discontinue if elevations persist. Six Lynavoy-treated patients (5%) discontinued for liver-test elevations vs 2% on placebo.
• Diarrhea — 62% vs 18% placebo; most often in the first 20 days; usually mild/moderate; 4% discontinued for diarrhea. Watch for dehydration (thirst, dry mouth, less urine, headache). Clinic may interrupt or stop if it persists.
• Fat-soluble vitamin deficiency (A, D, E, K) — check vitamins A/D/E and INR at baseline and periodically; supplement if deficient; consider stopping if deficiency persists despite supplements.
  • Bleeding — more frequent on Lynavoy (hemorrhage 9% vs 3%). Interrupt, evaluate for FSV deficiency, restart only when stable.
  • Bone fracture — IBAT inhibitors as a class have been associated with fractures; monitor bone health and FSV status.

Most common adverse reactions (≥5% and more than placebo): diarrhea, abdominal pain, nausea, increased ALT, hemorrhage, increased AST, headache, dyspepsia, GERD, abdominal distension, dizziness, arthralgia.

Discontinuations for AEs: 14% Lynavoy vs 5% placebo.

FDA postmarketing requirements explicitly call out liver injury, bone health, and bleeding (complete LLSAT) plus a pregnancy exposure study. That is regulator language for “we need more long-term safety data,” not an unlabelled ban.

Pregnancy / lactation: minimal systemic absorption expected; FSV monitoring matters for fetal/neonatal health. Pregnancy exposures: report via 1-844-782-4278 (current DailyMed).

Who is working on this

Questions to take to the clinic

1. Do I meet the labelled population — adult PBC with cholestatic pruritus — and do I have any decompensation history that would put me in the avoid group?
2. How will you schedule liver tests and fat-soluble vitamin / INR checks before and during treatment?
3. I already take cholestyramine / colesevelam / UDCA / other itch medicines — how do we time doses (especially the 4-hour resin separation)?
4. What is your plan if diarrhea starts in the first weeks — when do we interrupt vs stop?
5. In the United States, is a bottle actually available through our pharmacy / specialty channel this month (DailyMed marketing start was 11 Jun 2026)?
6. In the United Kingdom, is this a private or NHS path while NICE GID-TA11307 is still awaiting development?
7. In Canada, are we waiting for a Health Canada decision (SUR since 2025-08), or is there another documented pathway you recommend — without assuming SAP?
8. If I could become pregnant, how do we handle FSV monitoring and the pregnancy registry (1-844-782-4278 on the US label)?

What this is not

• Not a cure for PBC.
• Not a topical drug (the approval letter and USPI are oral tablets).
• Not a Health Canada authorisation yet.
• Not an EC / EU pack yet (CHMP opinion only).
• Not an NHS routine-funding yes (NICE awaiting development).
• Not a retrieved expanded-access or compassionate-use programme on the sources checked.
• Not a reason to stop UDCA or other disease-directed therapy without your clinician’s plan.
• Not medical advice.

Sources (primary first)

1. FDA NDA 220295 approval letter, 17 Mar 2026 — https://www.accessdata.fda.gov/drugsatfda_docs/nda/2026/220295Orig1s000Approv.pdf
2. DailyMed Lynavoy USPI, setid c00317c8-709c-4707-a6d1-632bff123026 (Intercept/Alfasigma pack; revised 6/2026; marketing 11 Jun 2026).
3. MHRA GOV.UK news, 1 May 2026 — https://www.gov.uk/government/news/mhra-approves-linerixibat-lynavoy-for-the-treatment-of-itch-due-to-biliary-tract-disease
4. EMA Lynavoy EPAR / CHMP opinion page — https://www.ema.europa.eu/en/medicines/human/EPAR/lynavoy (opinion 23 Jul 2026; EMEA/H/C/006241).
5. Health Canada SUR — New drug submissions under review (list current 2026-07-31): Linerixibat, accepted 2025-08, GlaxoSmithKline Inc.
6. NICE GID-TA11307 / ID6265 — https://www.nice.org.uk/guidance/awaiting-development/gid-ta11307
7. ClinicalTrials.gov NCT04950127 (GLISTEN); NCT04167358 (LLSAT).
8. Hirschfield GM et al. Lancet Gastroenterol Hepatol. 2026;11:22–33. DOI 10.1016/S2468-1253(25)00192-X (journal; not the label).