Elaspol (sivelestat) / Ono Pharmaceutical - LARVOL DELTA

Efficacy and Safety of Sivelestat Sodium in Patients with Acute Ischemic Stroke: A Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Study (ChiCTR) - P=N/A | N=8 | Not yet recruiting | Sponsor: Beijing Tiantan Hospital, Capital Medical University; Beijing Tiantan Hospital, Capital Medical University

New trial • Cardiovascular • Ischemic stroke

Efficacy and safety of application of Sivelestat in pediatric intensive care unit: a systematic review and meta‑analysis. (PubMed, Transl Pediatr) - "In pediatric patients with severe conditions such as ALI/ARDS, Sivelestat may improve the oxygenation index and inhibit the release of inflammatory mediators, but safety assessment remains limited. However, given the limited number of included studies and inter-study heterogeneity, large-scale trials are still needed to verify the results."

Journal • Retrospective data • Acute Lung Injury • Acute Respiratory Distress Syndrome • Critical care • Pediatrics • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL6 • TNFA

Innovations in Nanotechnology-based Drug Delivery for Ischemic Stroke. (PubMed, Curr Neuropharmacol) - "Endogenous cell-mediated transport(CMT) represents a superior strategy for traversing the blood-brain barrier in ischemic stroke, enabling the attainment of therapeutic drug concentrations at the lesion site while simultaneously mitigating systemic toxicity. Neutrophil-targeted nanotherapy-whether achieved through drug-loaded nanoparticle "hitchhiking" or the inhibition of neutrophil elastase-offers a paradigm-shifting approach to the treatment of acute ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • ELANE • IL17A

Sivelestat Sodium versus Standard Care for Prevention of Postoperative Lung Injury and Acute Respiratory Distress Syndrome in Adult Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass:A Systematic Review and Meta-Analysis. (PubMed, J Cardiothorac Vasc Anesth) - "Sivelestat shows consistent directional benefit in CPB-associated pulmonary outcomes, but heterogeneity limits statistical significance. Larger multicenter RCTs are needed to confirm efficacy and define clinical use."

Journal • Retrospective data • Review • Acute Lung Injury • Acute Respiratory Distress Syndrome • Cardiovascular • Critical care • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Systemic Inflammatory Response Syndrome • ELANE

Neutrophil serine proteases inhibit thermogenic capacity of visceral white adipose tissue. (PubMed, Nat Metab) - "Administration of sivelestat suppressed diet-induced neutrophil infiltration, enhanced cold-induced visceral fat browning and decreased visceral fat content in mice. These findings reveal an unexpected inhibitory role of NSPs in visceral fat browning and suggest the potential of repurposing sivelestat as an anti-obese drug."

Journal • Genetic Disorders • Obesity • CCND1 • CDK4 • ELANE • IGFBP3

PALETTE: Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial (clinicaltrials.gov) - P2 | N=2000 | Recruiting | Sponsor: Assistance Publique - Hpitaux de Paris | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Septic Shock

SivelSep: Phase IIb Multicenter Randomized Controlled Trial Evaluating the Efficacy of Sivelestat in Patients With Septic Coagulopathy (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: University Hospital, Strasbourg, France | Trial primary completion date: Dec 2032 ➔ Aug 2032 | Initiation date: Mar 2026 ➔ Aug 2027

Trial initiation date • Trial primary completion date • Hematological Disorders • Septic Shock

Development of atropisomeric 5N-sulfonyl-1,5-benzodiazepin-2-ones with high inhibitory activity against neutrophil elastase. (PubMed, RSC Med Chem) - "The eutomer exhibited approximately 10-fold higher inhibitory activity than the currently used lead compound sivelestat (ONO-0546) (1), indicating its potential as a treatment for acute lung injury. Docking studies with target proteins supported our hypothesis of high activity."

Journal • Acute Lung Injury • Respiratory Diseases • ELANE

The use of sivelestat sodium among patients with acute pancreatitis and early organ failure: a single-center retrospective cohort study. (PubMed, Front Med (Lausanne)) - "Sivelestat sodium use was associated with more organ failure-free days in patients with AP and early organ failure, particularly in those with respiratory failure. These findings require confirmation in future prospective randomized trials."

Journal • Retrospective data • Pancreatitis • Respiratory Diseases • CRP • ELANE

The neutrophil-NETs-elastase axis drives pulmonary lymphatic endothelial injury and aggravates acute lung injury. (PubMed, Int Immunopharmacol) - "DNase I or sivelestat treatment reduced pulmonary lymphatic injury and lung injury, with the combined treatment showing the strongest effect. RNA sequencing showed changes in inflammation-, stress-, and apoptosis-related pathways. In conclusion, activated neutrophils damage pulmonary lymphatic endothelium through NETs and NE, leading to impaired lymphatic drainage and worsened ALI."

Journal • Acute Lung Injury • Inflammation • Pulmonary Disease • Respiratory Diseases • ELANE

SIVAR-NMOSD: Safety and Efficacy Study of Sivelestat in Neuromyelitis Optica Spectrum Disorder (clinicaltrials.gov) - P1/2 | N=7 | Not yet recruiting | Sponsor: Kyushu University

New P1/2 trial • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Therapeutic Efficacy of Sivelestat Sodium in ARDS Following Aortic Dissection: A Pilot Physiological Trial with Exploratory Transcriptomic Analysis. (PubMed, J Inflamm Res) - "Exploratory transcriptomics identified six hub genes (BPI, ELANE, CEBPE, MPO, CTSG, DEFA3) implicating neutrophil protease-centered pathways. These findings support the need for larger, biomarker-integrated multicenter trials to confirm efficacy and define responsive subgroups."

Clinical • Journal • Acute Respiratory Distress Syndrome • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Systemic Inflammatory Response Syndrome • CRP • ELANE

A Novel IDO1/NE Dual Inhibitor, IMM-H018 Prevents the Primary and Secondary Sepsis and Ameliorates the Kidney Injury Through Inhibiting the Cytokine Storm and Microthrombosis, and Reversing Immunosuppression. (PubMed, Adv Sci (Weinh)) - "Combined treatment with the neutrophil elastase (NE) inhibitor Sivelestat and the indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor Epacadostat showed superior efficacy to either monotherapy in LPS- and CLP-induced septic mice. In a two-hit sepsis model, IMM-H018 prevented secondary infection, enhanced bacterial clearance through improved phagocytosis, protected against renal damage, and delayed progression from acute kidney injury to chronic kidney dysfunction. These findings identify IMM-H018 as a promising therapeutic candidate for sepsis and sepsis-associated kidney injury."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Hematological Disorders • Infectious Disease • Inflammation • Nephrology • Renal Disease • Septic Shock • Thrombosis • ELANE • IDO1

Sivelestat sodium alleviates sepsis-associated acute lung injury by inhibiting ferroptosis via the Nrf2/SLC7A11/GPX4 axis. (PubMed, PLoS One) - "Sivelestat sodium ameliorates SALI in rats by inhibiting ferroptosis through regulation of the Nrf2/SLC7A11/GPX4 signaling pathway."

Journal • Acute Lung Injury • Infectious Disease • Respiratory Diseases • Septic Shock • ACSL4 • GPX4 • IL1B • IL6 • SLC7A11 • TFRC • TNFA

Neutrophil-targeted nanoparticles delivering sivelestat alleviate cerebral ischemia-reperfusion injury by suppressing NETosis. (PubMed, Mater Today Bio) - "The therapeutic mechanism entails the suppression of NE-dependent NETosis coupled with a shift in microglial polarization toward the anti-inflammatory M2 phenotype, resulting in dual modulation of neuroinflammation. This study thus introduces a neutrophil-hitchhiking nanoplatform that synergistically disrupts the NE-NETs axis and reprograms the inflammatory microenvironment, presenting a transformative approach for the treatment of ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury • ELANE

Inhibition of elastin degradation alleviates joint degeneration in aging mice, dogs, and human models. (PubMed, Proc Natl Acad Sci U S A) - "Therapeutically, both the myeloid-specific knockout of neutrophil elastase and the pharmacological inhibition using a clinically applied drug (sivelestat) alleviated joint degeneration in naturally aging mice partly by reducing elastin fragments levels...Finally, several matrix fragments, including the fragments of type II collagen, fibronectin, hyaluronic acid, and aggrecan, were demonstrated to universally induce cartilage degeneration. Conclusively, this study identifies degraded matrix, especially elastin fragments, as one of the drivers of joint degeneration via pathological macrophage-chondrocyte crosstalk, suggesting elastase inhibitors as a potential therapeutic strategy for aging-related osteoarthritis."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • ACAN • ELANE • NEU1

Neutrophil extracellular traps drive cholangiocyte injury via ZNF709-TP53-MDM2 pathway in primary biliary cholangitis. (PubMed, Hepatol Int) - "These findings identify a resistin-NETs-ZNF709 axis that links neutrophil activation to cholangiocyte injury in PBC and suggest that targeting NETs-associated injury with sivelestat may represent a potential strategy to improve current PBC therapies."

Journal • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Primary Biliary Cholangitis • ELANE • RETN

Choline supplementation protects against sepsis-induced lung injury, potentially through suppression of Prtn3-associated monocyte activation. (PubMed, Front Pharmacol) - "Conversely, pharmacological inhibition of Prtn3 by sivelestat suppressed inflammatory cytokine expression and attenuated NF-κB signaling under LPS-stimulated conditions. Choline supplementation protects against SLI by suppressing monocyte inflammatory activation, at least in part through inhibition of the Prtn3-dependent NF-κB signaling pathway. These findings suggest that targeting the choline-Prtn3-NF-κB axis may represent a potential therapeutic strategy for sepsis-associated lung injury."

Journal • Hematological Disorders • Infectious Disease • Inflammation • Respiratory Diseases • Septic Shock • IL1B • IL6 • TNFA

Sivelestat sodium alleviates blood brain barrier dysfunction after traumatic brain injury by reduction of NETs formation. (PubMed, Exp Neurol) - "This study suggests that sivelestat sodium protects the BBB and mitigates TBI-related injury by suppressing NETs formation and subsequent vascular endothelial pyroptosis, highlighting its therapeutic potential."

Journal • CNS Disorders • Vascular Neurology • ELANE • GSDMD • TJP1

Sivelestat Sodium as an Adjunct to Endovascular Thrombectomy for Acute Anterior Circulation Large-Vessel Occlusion (clinicaltrials.gov) - P=N/A | N=868 | Recruiting | Sponsor: Xuanwu Hospital, Beijing | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

Ferritin Nanoparticle-Mediated Sustained Delivery of Sivelestat with Poor Water Affinity Attenuates Acute Lung Injury via Dual Inhibition of NETs and Pyroptosis. (PubMed, ACS Appl Mater Interfaces) - "It effectively reduced pulmonary oxidative stress, inhibited neutrophil infiltration and proinflammatory cytokine release, and alleviated lung injury by inhibiting the NLRP3/GSDMD pyroptosis pathway. Collectively, the findings provide compelling experimental evidence supporting the development of ferritin-based nanomedicine as an efficient and safe therapeutic approach for ALI."

Journal • Acute Lung Injury • Respiratory Diseases • NLRP3

Efficacy and optimal timing of sivelestat in critically ill patients with COVID-19: a multicenter retrospective cohort study. (PubMed, BMC Pulm Med) - "Our study suggests that sivelestat use may be associated with reduced 28-day mortality in ICU patients with severe COVID-19."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Critical care • Gastroenterology • Hematological Disorders • Hepatology • Infectious Disease • Liver Failure • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Septic Shock • Thrombosis

PD05, a novel neutrophil elastase inhibitor, mitigates LPS-induced acute lung injury in a preclinical model. (PubMed, Pulm Pharmacol Ther) - "However, currently available NE inhibitors such as Sivelestat have shown limited clinical efficacy...Histological analysis further confirmed reduced lung injury and improved epithelial integrity in PD-05-treated mice. Collectively, PD-05 exerts coordinated anti-inflammatory and barrier-protective effects in experimental ALI, underscoring its translational potential for ALI and ARDS."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • ELANE • HIF1A • HMOX1 • ICAM1 • IL6 • SFTPC • TNFA

A near-infrared fluorescent probe for monitoring of elastase activity in diabetes and inflammatory models. (PubMed, Talanta) - "Conversely, when cells were pretreated with the inhibitor sivelestat, the fluorescence signal was markedly attenuated...The Probe was also utilized for fluorescence optical imaging analysis of liver and kidney tissue sections; relative to the group treated with insulin, the diabetic group that received no pharmacological intervention exhibited significantly stronger fluorescence signals. Consequently, YZ5F provides a solid foundation for the early diagnosis, therapeutic efficacy assessment, and drug screening associated with inflammation-related diseases and diabetes."

Journal • Diabetes • Inflammation • Metabolic Disorders • ELANE

Unraveling signaling pathways involved in epithelial-mesenchymal transition triggered by Neutrophil Extracellular Traps (NETs) in cancer cells (EACR 2026) - "Two EGFR-driven lung cancer cell lines, namely H1975 and HCC827, were treated with NETs in the presence or absence of Sivelestat, a neutrophil elastase inhibitor, in both dose-dependent (0.5uM-10uM) and time-dependent (24h-48h) manner, followed by evaluation of EMT markers... Our findings, taken together, indicate that neutrophil elastase may trigger the intracellular signaling of NETs probably by causing E-cadherin cleavage and subsequent release of β-catenin from the plasma membrane to the cytoplasm. β-catenin from the cytoplasm may translocate to the nucleus and upregulate Notch 1 that in turn may activate EMT."

Lung Cancer • Oncology • Solid Tumor • CDH1 • EGFR • ELANE • NOTCH1 • VIM