tigulixostat (LC350189) / LG Chem, Innovent Biologics - LARVOL DELTA

Tigulixostat (IBI128) vs Febuxostat in Gout (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Innovent Biologics Technology Limited (Shanghai R&D Center) | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Innovent Biologics…announced that the xanthine oxidase inhibitor (XOI) Tigulixostat(R&D code: IBI128) have the first participant dosed in a Phase 3 clinical study in head-to-head comparison of febuxostat, aiming to provide a better treatment option for Chinese gout patients (PRNewswire) - "This study adopts a randomized, double-blind, multi-center Phase 3 design, and plans to enroll 600 Chinese patients who meet the 2015 ACR/EULAR gout diagnostic criteria, and randomize them in a 1:1 ratio to receive tigulixostat 100 mg or febuxostat 40 mg for 24 weeks."

Trial status • Gout

Tigulixostat (IBI128) vs Febuxostat in Gout (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Innovent Biologics Technology Limited (Shanghai R&D Center)

New P3 trial • Gout • Inflammatory Arthritis • Rheumatology

A Phase I Dose-Escalation Study of the Pharmacokinetics, Pharmacodynamics, and Safety of a Single Oral Dose of Tigulixostat. (PubMed, Drug Des Devel Ther) - "The PK profile of GD-MET-1 indicated lower systemic exposure and less consistent dose proportionality compared with the parent compound, suggesting a supportive rather than dominant role in PD activity. The favorable safety and tolerability profile reinforces tigulixostat's potential as a novel therapeutic agent for the management of hyperuricemia."

Journal • P1 data • PK/PD data

Gout therapy updated. (PubMed, Ther Adv Musculoskelet Dis) - "This article will also serve as a review of current urate-lowering pharmacological options including xanthine oxidase inhibitors, uricosurics, and uricase therapy as well as burgeoning new medications on the horizon including novel potent xanthine oxidase inhibitors (including tigulixostat), sodium-glucose transporter-2 inhibitors, and selective URAT1 inhibitors. Additionally, this article will review pharmacological approaches to treating gout flares (including nonsteroidal anti-inflammatory drugs, glucocorticoids, and colchicine) and discuss the role of patient comorbidities in selection of optimal therapy. The present review will also discuss the role and limitations of novel interleukin-1 (IL-1) antagonists (including anakinra and canakinumab) in the treatment of gout flares. Lastly, this article will also discuss nonpharmacological intervention for gout management and discuss novel therapies for chronic gout management, gout flare, and prophylaxis on the horizon."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Genetic Disorders • Gout • Hypertension • Immunology • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Obesity • Pain • Renal Disease • Rheumatology

EURELIA1: Tigulixostat, Phase 3 Study, Placebo Controlled in Gout Patients (clinicaltrials.gov) - P3 | N=354 | Completed | Sponsor: LG Chem | Recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Dec 2024

Trial completion • Trial completion date • Gout • Inflammatory Arthritis • Rheumatology

EURELIA2: Tigulixostat, Phase 3 Study, Allopurinol Controlled in Gout Patients (clinicaltrials.gov) - P3 | N=2202 | Completed | Sponsor: LG Chem | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ May 2025

Trial completion • Trial completion date • Gout • Inflammatory Arthritis • Rheumatology

A Dose Finding Study to Assess Efficacy and Safety of IBI128 in Chinese Gout Subjects (clinicaltrials.gov) - P2 | N=84 | Completed | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Active, not recruiting ➔ Completed

Trial completion • Gout • Inflammatory Arthritis • Rheumatology

Evaluation of the efficacy and safety of a novel xanthine oxidase inhibitor, tigulixostat, in gout patients with hyperuricemia: Design of the EURELIA 1 and EURELIA 2 studies. (PubMed, Contemp Clin Trials) - P3 | "EURELIA 1 and EURELIA 2 studies will be able to adequately determine the efficacy and safety of tigulixostat compared to both placebo and allopurinol."

Journal • Gout • Inflammatory Arthritis • Rheumatology

Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization. (PubMed, J Inflamm Res) - "In this study, we discovered that Tigulixostat (LC350189) more effectively reduced SUA levels and resulted in better renal outcomes compared to allopurinol, without inducing liver injury in urate oxidase knockout (Uox-KO) mice. Mechanistically, we found that Tigulixostat improved HN by promoting M2 macrophage polarization. These findings suggest Tigulixostat as a promising therapeutic option for managing hyperuricemia and related kidney conditions."

Journal • Hepatology • Liver Failure • Nephrology • Renal Calculi • Renal Disease

Pharmacokinetics and Pharmacodynamics of Tigulixostat in Participants with Mild, Moderate, and Severe Renal Impairment (ACR Convergence 2024) - P1 | "Tigulixostat exposure and sUA reduction efficacy were not significantly different between participants with various degrees of renal impairment and those with normal renal function. Therefore, tigulixostat is not expected to require dose adjustment in patients with mild, moderate, or severe renal impairment, and multiple doses of tigulixostat were found to be safe and generally well-tolerated in these participants. Figure 1."

PK/PD data • Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology

A Dose Finding Study to Assess Efficacy and Safety of IBI128 in Chinese Gout Subjects (clinicaltrials.gov) - P2 | N=84 | Active, not recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Gout • Inflammatory Arthritis • Rheumatology

A Dose Finding Study to Assess Efficacy and Safety of IBI128 in Chinese Gout Subjects (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

New P2 trial • Gout • Inflammatory Arthritis • Rheumatology

PRECLINICAL IN VITRO AND IN VIVO EFFICACY STUDIES OF TIGULIXOSTAT, A SELECTIVE NON-PURINE XANTHINE OXIDASE INHIBITOR (EULAR 2024) - "Xanthine oxidase (XO) inhibitors, such as allopurinol (ALO) and febuxostat (FBX), are the current standard of care for lowering serum urate levels in patients with gout. In preclinical evaluation of efficacy, TGX inhibited XO enzyme activity and lowered uric acid at a level comparable to febuxostat. In addition, TGX, with no structural resemblance to purine base, does not affect the pyrimidine metabolism and its related kidney toxicity in mice."

Preclinical • Gout • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatology

A Study to Investigate the Pharmacokinetic/Pharmacodynamic Characteristics of IBI128(A New Xanthine Oxidase Inhibitor) (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Mar 2024

Trial completion • Trial completion date • Gout • Immunology • Inflammatory Arthritis • Rheumatology

A Study to Investigate the Pharmacokinetic/Pharmacodynamic Characteristics of IBI128(A New Xanthine Oxidase Inhibitor) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

New P1 trial • Gout • Immunology • Inflammatory Arthritis • Rheumatology

Comment on serum urate-lowering efficacy and safety of Tigulixostat in gout patients with hyperuricemia: A randomized, double-blind, placebo-controlled, dose-finding trial. (PubMed, Int J Rheum Dis) - No abstract available

Clinical • Journal • Gout • Inflammatory Arthritis • Rheumatology

Effect of Tigulixostat on the Pharmacokinetics of Theophylline (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: LG Chem

New P1 trial • Gout • Inflammatory Arthritis • Rheumatology

Pipeline Therapies for Gout. (PubMed, Curr Rheumatol Rep) - "Dotinurad may function in the setting of decreased renal function. Arhalofenate has anti-URAT-1 activity and may also blunt gout flares. A new xanthine oxidase inhibitor (XOI), tigulixostat, is under study...Dapansutrile, an oral agent under investigation, inhibits activation of the NLRP3 inflammasome and may be an effective anti-inflammatory. New treatments for gout that are under study may work in the setting of comorbidities, simplify management, utilize new mechanisms, or have reduced side effects."

Journal • Review • Gout • Inflammatory Arthritis • Nephrology • Renal Calculi • Renal Disease • Rheumatology • IL1B • NLRP3

A&R Paper 1: Serum urate-lowering efficacy and safety of tigulixostat in gout patients with hyperuricemia: a randomized, double-blind, placebo-controlled, dose-finding trial (CLUE) (EULAR 2023) - No abstract available

Clinical • Gout • Inflammatory Arthritis • Rheumatology

EURELIA2: Tigulixostat, Phase 3 Study, Allopurinol Controlled in Gout Patients (clinicaltrials.gov) - P3 | N=2542 | Recruiting | Sponsor: LG Chem | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

"📑ECA fase 2 muestra eficacia significativa de tigulixostat frente a placebo en reducción de uricemia en #gota 🎯Úrico <5 mg/dl a 12 semanas: -Placebo: 2.9% -TGX 50: 47.1% -TGX 100: 44.7% -TGX 200g: 62.2% #gout #uricacid #tigulixostat @geacser @KenSaag https://t.co/1uXyWbJzbk" (@enriquecalvoA)

Clinical • Gout • Inflammatory Arthritis • Rheumatology

LG Chem aims to release four new drugs by 2030 after Aveo acquisition deal closure (Korea Biomedical Review) - "LG Chem said on Thursday that it invested 707.2 billion won ($571 million) to complete the acquisition of Aveo Pharmaceuticals, a U.S. oncology-specializing biopharma firm, through LG Chem Life Science Innovation Center, and will finalize the last details of the merger on Friday this week....Through the acquisition of Aveo, LG Chem plans to transfer the new anticancer drug pipeline developed by LG Life Sciences to Aveo in the mid-to-long term to accelerate the commercialization of new anticancer drugs in the U.S....To secure global competitiveness through global new drugs, the company will invest 2 trillion won in R&D from this year by 2027 to release at least four new drugs in the field of anticancer and metabolic disease in the U.S. and other global markets by 2030....This includes late-stage drugs from Aveo’s anticancer pipeline such as ficlatuzumab together with LG Chem’s LC350189 (ingredient: tigulixostat) for gout."

M&A • Gout • Oncology

EURELIA1: Tigulixostat, Phase 3 Study, Placebo Controlled in Gout Patients (clinicaltrials.gov) - P3 | N=350 | Recruiting | Sponsor: LG Chem | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Serum urate-lowering efficacy and safety of tigulixostat in gout patients with hyperuricemia: a randomized, double-blind, placebo-controlled, dose-finding trial (CLUE). (PubMed, Arthritis Rheumatol) - "Tigulixostat significantly lowered sUA levels compared to placebo at all doses used with an acceptable safety profile."

Clinical • Journal • Gout • Inflammatory Arthritis • Rheumatology