Delving into the Latest Updates on Linerixibat with Synapse

This is a phase 1, open-label, single-dose study in adults with moderate hepatic impairment (defined as Child-Pugh B cirrhosis) and matched healthy control participants with normal hepatic function. All participants in both cohorts (moderate hepatic impairment and matched healthy controls) will receive a single dose of the study drug, linerixibat. The purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (PK) and safety of linerixibat.

Start Date19 Jul 2022

Sponsor / Collaborator

GSK Plc

NCT05133830

/ CompletedPhase 1

A Two-part, Phase 1, Open-label, Randomized, Parallel-arm, Fixed Sequence, Drug-drug Interaction Study to Investigate the Effect of Linerixibat on Plasma Concentrations of Obeticholic Acid and Conjugates in Healthy Adult Participants

This study aims to investigate the effect of linerixibat on plasma concentrations of obeticholic acid (OCA) and its conjugates in healthy adult participants to inform the potential for drug interaction with coadministration of linerixibat and OCA.

Start Date23 Nov 2021

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with Linerixibat

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100 Translational Medicine associated with Linerixibat

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100 Patents (Medical) associated with Linerixibat

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38

Literatures (Medical) associated with Linerixibat

01 Mar 2026·The Lancet Gastroenterology & Hepatology

Antipruritic effects of the ileal bile acid transporter inhibitor linerixibat

Letter

Author: Kremer, Andreas E ; Levy, Cynthia ; Hirschfield, Gideon M

01 Jan 2026·The Lancet Gastroenterology & Hepatology

Linerixibat in patients with primary biliary cholangitis and cholestatic pruritus (GLISTEN): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial

Article

BACKGROUND:

Cholestatic pruritus is common and undertreated in primary biliary cholangitis (PBC) and negatively affects patients' lives. We aimed to evaluate the safety and efficacy of linerixibat, an ileal bile acid transporter inhibitor, as a specific antipruritic therapy in patients with PBC.

METHODS:

We conducted a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Patients with PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥4) were recruited at 115 centres in 19 countries. Patients were randomly assigned to receive either oral linerixibat 40 mg twice a day or a matching placebo through an interactive online response system, with pruritus severity (moderate or severe) and concomitant pruritus treatment (bile acid binding resins, other treatments, or none) as stratification factors. The primary endpoint was change in pruritus over 24 weeks assessed using the WI-NRS, ranging from 0 (no itching) to 10 (worst imaginable itching). Efficacy analyses included all randomly allocated patients; safety analyses included all randomly allocated patients who received one dose of study treatment or more. This study is registered with ClinicalTrials.gov, number NCT04950127.

FINDINGS:

From Dec 1, 2021, to May 13, 2024, a total of 238 patients were randomly assigned to receive either linerixibat (n=119) or placebo (n=119). One (<1%) of 119 patients randomly allocated to receive placebo withdrew before receiving treatment. Patients receiving linerixibat experienced significant improvement in pruritus over 24 weeks compared with placebo (least-squares mean change from baseline -2·86 [95% CI -3·23 to -2·50] for linerixibat vs -2·15 [-2·51 to -1·78] for placebo; adjusted mean difference -0·72 [95% CI -1·15 to -0·28]; p=0·0013). Gastrointestinal adverse events were more frequent in patients treated with linerixibat than with placebo (72 [61%] of 119 vs 21 [18%] of 118 had diarrhoea; 22 [18%] vs four [3%] had abdominal pain). Treatment discontinuations due to gastrointestinal adverse events occurred in eight (7%) of 119 patients in the linerixibat group (of which five were due to diarrhoea) and one (<1%) of 118 in the placebo group. Serious adverse events were reported in 14 (12%) of 119 patients receiving linerixibat and four (3%) of 118 receiving placebo. No deaths were reported during the study.

INTERPRETATION:

Linerixibat significantly improved pruritus versus placebo, supporting its potential to address a major symptom of PBC. An expected increase in diarrhoea in linerixibat-treated patients was observed.

FUNDING:

GSK.

01 Dec 2025·Gastroenterology & hepatology

Impact of Linerixibat on Pharmacodynamic Biomarkers and Mediators of Cholestatic Pruritus in PBC in the Phase 3 GLISTEN Study.

Article

23

News (Medical) associated with Linerixibat

31 Mar 2026

·www.biospace.com

Alfasigma Reports Solid Performance in 2025 Supported by Double-Digit Revenue Growth in key strategic brands in Immunology (+17%1), Gastroenterology (+15%), Vascular (+10%), and Consumer Healthcare expansion portfolio in international markets

Revenues of €1.8 billion (-4% versus PY) driven by solid performance across key therapeutic areas and global markets, partially offset by Ocaliva® withdrawal impact. Adjusted EBITDA 2 of €350 million (-18% versus PY) underpinned by streamlined operational efficiencies and operating model evolution. Like-for-like Revenues up 7%, and EBITDA up 20%, adjusted for voluntarily withdrawal of Ocaliva® from US market. Marketing application under EMA review for the use of Jyseleca® in a new indication of axial spondyloarthritis (axSpA), a chronic inflammatory arthritis, to address unmet patient needs, submitted following the reporting period. Following the reporting period, agreement with GSK plc for worldwide exclusive rights to develop, manufacture and commercialise linerixibat; subsequently granted FDA approval for the US market (March 2026). BOLOGNA, Italy--(BUSINESS WIRE)--Alfasigma S.p.A (“Alfasigma” or the “Company”), a global pharmaceutical company founded over 75 years ago in Italy, where it is headquartered, today announced its financial results for the fiscal year 2025. Its results reflect a year of strategic evolution and solid performance of key brands – all contributing to market share growth. Despite its voluntary withdrawal of Ocaliva® from the US market, Alfasigma delivered strong performance through its disciplined investment strategy and effective execution, unlocking opportunities and building momentum across its key therapeutic areas (gastroenterology, vascular & immunology) and consumer healthcare. Growing Performance Across Products and Markets Alfasigma saw double-digit growth from many of its brands namely Vessel®, Normix® and Jyseleca® and the Esoxx (reflux) brand family. Similarly, Alfasigma saw significant growth across its Growth Markets (+15% vs PY) and Western Europe (+11% 1 vs PY) segments, from investments in expanded commercial teams, targeted media spend, and new affiliates leading to the increase in market share. Over 2025, the Company added new locations (KSA and Hungary) bringing its products to more patients worldwide. Continued investments to expand Innovative Portfolio Investment partnerships were announced following the reporting period, including the March 2026 agreement with GSK plc for the worldwide exclusive rights to develop, manufacture and commercialise linerixibat, an investigational ileal bile acid transporter (IBAT) inhibitor being developed for the treatment of cholestatic pruritus in primary biliary cholangitis (PBC). Subsequently granted approval by the US FDA becoming the first medicine approved in the US for this indication. The approval, based on the positive GLISTEN phase III trial, provides immediate commercialisation opportunities in the US, with regulatory reviews underway in the EU, UK, Canada and China 3 . Additionally, in January 2026, Alfasigma announced its investment in Innovative Molecules, obtaining the exclusive worldwide license to the parenteral formulation of adibelivir for the treatment of Herpes Simplex Virus (HSV) encephalitis, an ultra-rare and life-threatening condition. The company is well-positioned to drive future organic growth as well through expanding its pipeline of opportunities. This includes delivering on the full potential of Jyseleca®, with application submitted following the reporting period, and being under review by EMA for the use of Jyseleca® in a new indication of treatment for axial spondyloarthritis (axSpA), a chronic inflammatory arthritis primarily affecting the spine and sacroiliac joints, causing chronic pain and stiffness that often begins in early adulthood. A disease with high prevalence in Europe, only around 40-50% of patients with axSpA achieve an adequate response with current advanced therapies, highlighting significant unmet needs. Chairman Stefano Golinelli stated, “ I am proud of our progress over 2025. We delivered solid results, advancing our strategy to drive sustainable growth and to develop meaningful solutions to patients worldwide. Alfasigma’s continued investment in innovation, partnerships, talent, capabilities, and our portfolio, positions the Company for even greater success in the years ahead .” CEO Francesco Balestrieri commented, “ Our 2025 financial results are testament to Alfasigma’s strategic direction, reflecting the strength of our existing and expanding product portfolio, particularly across Growth Markets. The US and Italy remain important markets, and the Company’s performance shows that where we invest, we grow. We are financially strong and well-capitalised, underpinning our capacity to invest across key markets and products with potential – at pace and with agility – as we advance our portfolio for continued profitable growth .” Capitalised for Future Growth Over 2025, Alfasigma completed successful financing rounds to support its R&D, and to accelerate growth, transformation, and global expansion. This included, but was not limited to, European Investment Bank and SACE, as well as several Italian private banks. Forward Momentum and Sustainable Growth Looking ahead, Alfasigma is well-placed to capitalise on its 2025 performance. Today, the company is in a significantly stronger position, with revamped growth in Consumer Healthcare and Established platforms, as well as new Rare and Specialty platforms. Leveraging its portfolio and growing presence across markets worldwide, Alfasigma is equipped to drive future growth and offer significant headroom for value creation through a disciplined M&A strategy. About Alfasigma Alfasigma is a global pharmaceutical company founded over 75 years ago in Italy, where it is headquartered today in Bologna and Milan. The Group’s products are distributed in more than 100 markets worldwide. Alfasigma operates offices across major European countries, as well as in the United States, China, and Mexico; production facilities in Italy, Spain, and the United States; and R&D laboratories located in Italy. The company employs approximately 4,000 professionals dedicated to the research, development, production, and distribution of medicinal products. Its portfolio ranges from consumer healthcare products and primary care treatments to specialty and rare disease medications, with key therapeutic areas including gastroenterology, vascular health, and immunology. 1 Like-for-like comparison considering Jyseleca® business acquisition timing in 2024. 2 Adjusted EBITDA - adjusted EBITDA excludes the impact of restructuring costs and selected items related to Jyseleca® business acquisition. 3 This transaction is ongoing and is subject to customary conditions, including applicable regulatory agency clearances such as under the Hart-Scott-Rodino Act in the US. Contacts For further information, contact: Global Press office: Tristan Peniston-Bird tristan.peniston-bird@omc.com Irene Lawlor Irene.Lawlor@alfasigma.com

Drug ApprovalLicense out/inPhase 3BiosimilarFinancial Statement

19 Mar 2026

·www.fiercepharma.com

After Alfasigma's GSK licensing deal, Lynavoy picks up FDA nod in rare liver disease

The approval of Lynavoy comes a few days ahead of the FDA's March 24 decision target date. Alfasigma’s buzzer-beater bet on GSK’s rare liver disease prospect has paid off. After inking a deal worth up to $690 million to take on worldwide rights to the med last week, the FDA has doled out an approval a few days ahead of schedule.The drug, approved under the moniker Lynavoy, is an ileal bile acid transporter inhibitor that was designed to reduce multiple drivers of chronic itch. With the approval, the med is in position to reach the 89% of people with primary biliary cholangitis (PBC) who experience cholestatic pruritus, an often debilitating itching condition. The FDA signed off on the med a few days ahead of its March 24 decision target date based on GSK’s phase 3 Glisten trial, which showed Lynavoy significantly improved itch symptoms versus placebo over 24 weeks. Despite handing Lynavoy off to Alfasigma on March 9, the nod is still a milestone moment for GSK, as it represents “the first liver medicine from our pipeline to receive approval,” Kaivan Khavandi, M.D., Ph.D., GSK’s head of R&D for respiratory, immunology and inflammation, said in a company release.While “proud of the role” GSK played in discovering and developing the drug, the British pharma giant ultimately landed on Alfasigma as “the right partner to take this medicine forward” based on the Italian pharma’s experience in the PBC space, GSK’s chief scientific officer Tony Wood, Ph.D., explained at the time. Through the deal, GSK earned an upfront payment of $300 million plus an extra $100 million upon the FDA approval. The company is also in line for $20 million related to overseas regulatory approvals, plus up to $270 million in sales-based milestone payments and tiered double-digit royalties on net sales worldwide. The transaction has not yet closed, and Alfasigma is still “working closely with GSK,” it said in its own Thursday release. Alfasigma considers itself “uniquely positioned” to lead the worldwide commercialization of Lynavoy, given its “deep hepatology expertise and strong global footprint,” CEO Francesco Balestrieri said of the deal. The company’s PBC experience stems from its 2023 $800 million buyout of Intercept Pharmaceuticals, which was inked after years of struggles for Intercept and its PBC med Ocaliva. After winning an accelerated approval for the treatment in 2016, Intercept’s attempts to grow the med with a full approval and with an expansion into metabolic dysfunction-associated steatohepatitis were both shot down multiple times. The drug fully sputtered out last year, when Intercept acquiesced to the FDA’s requests to withdraw Ocaliva from the market following continued safety concerns.Some six months later, Aflasigma will make its comeback in the PBC space through Lynavoy. With Ocaliva out of the race, the drug enters a market populated by Ipsen’s Iqirvo and Gilead Sciences’ Livdelzi, both of which hit the market in 2024. Both companies have been recently reaping the benefits of the extra room in the PBC space, with Gilead reporting higher demand due to the Ocaliva withdraw and Ipsen touting growing momentum based on Ocaliva patient switches. Iqirvo garnered 77 million euros ($88.6 million) during the fourth quarter of 2025, while Livdelzi picked up $150 million.Lynavoy, meanwhile, is poised to corner a different core group of PBC patients with its cholestatic-pruritus-specific label. The condition can occur at any stage of the liver disease and has been “underestimated and overlooked for far too long, despite its significant impact on people living with PBC,” president of the PBCers Organization, Carol Roberts, noted in GSK’s release.

Phase 3License out/inDrug ApprovalClinical ResultAcquisition

19 Mar 2026

·endpoints.news

FDA approves GSK liver drug at center of Alfasigma deal

GSK’s recent deal to license out a rare liver disease drug just got sweeter. The FDA on Thursday approved linerixibat to treat cholestatic itch in patients with the autoimmune liver disease primary biliary cholangitis, or PBC. The approval makes GSK eligible for a $100 million payment under a deal announced earlier this month that would give rights to Italian pharma Alfasigma. The deal has yet to close. GSK will also get $300 million upfront, and there’s still $20 million on the table if linerixibat gets approved in the UK and Europe, plus another $270 million in milestones and certain royalties on global sales. The approval will likely fill a gap in Alfasigma’s commercial portfolio, after its subsidiary Intercept Pharmaceuticals pulled PBC drug Ocaliva from the market last year. Linerixibat will be marketed as Lynavoy. GSK did not immediately respond to a request for comment on pricing. GSK said its drug led to a “rapid, significant and sustained” improvement in itch compared to placebo in the Phase 3 GLISTEN trial. PBC is associated with a relentless itch that feels like it’s under the skin. The British pharma has estimated that 510,000 patients globally will have PBC by 2030, and just under half of those patients will experience a severe enough itch to require specific treatment.

Drug ApprovalPhase 3Accelerated ApprovalClinical Result

100 Deals associated with Linerixibat

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KEGG	Wiki	ATC	Drug Bank
D11539	-	-	DB11729

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Cholestatic pruritus	United States	GlaxoSmithKline LLC	17 Mar 2026

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Primary Biliary Cholangitis	Phase 3	United States	GlaxoSmithKline (Ireland) Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	United States	GlaxoSmithKline (China) Investment Co., Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Japan	GlaxoSmithKline (China) Investment Co., Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Japan	GlaxoSmithKline (Ireland) Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Argentina	GlaxoSmithKline (Ireland) Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Argentina	GlaxoSmithKline (China) Investment Co., Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Belgium	GlaxoSmithKline (China) Investment Co., Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Belgium	GlaxoSmithKline (Ireland) Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Brazil	GlaxoSmithKline (China) Investment Co., Ltd.	27 Aug 2021
Primary Biliary Cholangitis	Phase 3	Brazil	GlaxoSmithKline (Ireland) Ltd.	27 Aug 2021

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04950127 (GLISTEN, FDA_CDER) Manual	Phase 3	Primary Biliary Cholangitis	238	LYNAVOY	cxuvcemrjy(npjrntsmfe) = egejtkuyxk wwoimywzvf (xcjgufzwqg, 0.19) View more	Positive	17 Mar 2026
				placebo	cxuvcemrjy(npjrntsmfe) = eqmhvvwglf wwoimywzvf (xcjgufzwqg, 0.18) View more
NCT04950127 (GLISTEN, Pubmed \| Lancet Gastroenterol Hepatol)	Phase 3	Cholestatic pruritus \| Primary Biliary Cholangitis	238	Linerixibat 40 mg	aqovsqdjol(xjmnuwstsy) = unzkvtnvcv onvwhdxxvu (odiiamgzlx ) View more	Positive	01 Oct 2025
				Placebo	aqovsqdjol(xjmnuwstsy) = kcnfuablqn onvwhdxxvu (odiiamgzlx ) View more
NCT04950127 (GLIMMER \| GLISTEN, CTgov)	Phase 3	Cholestatic pruritus	238	Linerixibat (Part A: Linerixibat 40 Milligrams (mg))	qnyaepgfij(hlhbfsfurl) = iaiknhweem pmhecbsguf (rycywioybg, hwvmokqrfq - qnvtdclvaq) View more	-	22 Jul 2025
				Placebo+Linerixibat (Part A: Placebo)	qnyaepgfij(hlhbfsfurl) = aakuyvcogb pmhecbsguf (rycywioybg, xejuefhkik - kyfpulogbe) View more
NCT04950127 (GLISTEN, Company_Website 1 \| Company_Website 2) Manual	Phase 3	Primary Biliary Cholangitis	238	Linerixibat	iyefxnuxaw(hyhomfapat): Difference (LS Mean) = -0.72 (95% CI, -1.15 to -0.28), P-Value = 0.001 Met View more	Positive	19 Nov 2024
				Placebo
NCT04053023 (CTgov)	Phase 1	Cholestasis	19	OCA (Part A: OCA 10 mg)	aytdxfteiq(hcctfgkaqz) = mjmqepabxs zqzshcqueb (olamgsydyv, 43.54) View more	-	24 Jul 2020
				OCA+Linerixibat (Part A: OCA 10 mg + Linerixibat 90 mg)	cpaxvgqukh(ecavorabky) = lisndkhess niejpwonfo (gwhpzdilte, 55.81) View more
NCT03992014 (CTgov)	Phase 1	Cholestasis	6	[14C] Linerixibat+Linerixibat (Linerixibat 90 mg Oral Tablets + [14C] Linerixibat 100 μg IV)	ejzwsdoecs(bxpnswuknv) = lkyuooylwa bwksvyylee (hjvyzjzxnl, 25.8) View more	-	26 Jun 2020
				[14C]-Linerixibat ([14C]-Linerixibat 90 Milligram Oral Solution)	tldhdchbot(nyrkbclygz) = nhetpqcmpi eoztblpbho (qgpiufhjpk, 95.3) View more
NCT02202161 (CTgov)	Phase 2	Diabetes Mellitus, Type 2	70	placebo+metformin+GSK2330672 (Placebo)	qshmdpxgfz(mklwolhvet) = gqcetnthwk bzvdmzuutm (zatifrmawq, 16.357) View more	-	06 Nov 2017
				GSK2330672 (GSK2330672 10 mg BID)	qshmdpxgfz(mklwolhvet) = brqcbpxdiw bzvdmzuutm (zatifrmawq, 6.500) View more
NCT01929863 (CTgov)	Phase 2	Diabetes Mellitus, Type 2	16	Metformin+GSK2330672 (Treatment A-GSK2330672 + Metformin)	nhxagjsgfy = coucbeagai ynjnilxzjc (opoettscmg, aggicrdliy - owxfgvvwwt) View more	-	16 Aug 2017
				Placebo+Metformin (Treatment B-Placebo + Metformin)	nhxagjsgfy = junfilmgax ynjnilxzjc (opoettscmg, qhcsyudgwx - ngfnjssnhi) View more
NCT01899703 (Pubmed \| Lancet) Manual	Phase 2	Pruritus \| Primary Biliary Cholangitis	22	GSK2330672	kzxcplcfti(hinhudwvkt) = Diarrhoea was the most frequent adverse event during treatment with GSK2330672 (seven with GSK2330672 vs one with placebo) and headache was the most frequent adverse event during treatment with placebo (seven with placebo vs six with GSK2330672). opusieqolp (zpxemtxick )	Positive	18 Mar 2017
				Placebo