- |||||||||| Review, Journal: Targeting alarmins in asthma- From the bench to the clinic. (Pubmed Central) - Apr 5, 2025
In this review we discuss our current understanding of alarmin biology with a primary focus on allergic airway diseases. We link the mechanistic corollaries to the clinical implications and advances in drug development targeting alarmins-focusing on currently approved treatments, those under study, as well as future potential targets in the alarmin signaling pathways.
- |||||||||| itepekimab (SAR440340) / Sanofi, Regeneron, Fasenra (benralizumab) / AstraZeneca, brensocatib (INS1007) / Insmed
Review, Journal: Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review. (Pubmed Central) - Oct 7, 2024 Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab).
- |||||||||| itepekimab (SAR440340) / Sanofi, Regeneron
Enrollment closed: AERIFY-1: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - Jul 12, 2024 P3, N=960, Active, not recruiting, Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting
- |||||||||| Clinical, Journal: Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins. (Pubmed Central) - Jul 2, 2024
300 eosinophils/?L treated with dupilumab (anti-IL-4R?)...Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD.
- |||||||||| SAR445399 / Sanofi
SAR445399 () - Nov 6, 2023 - Abstract #ISDS2023ISDS_354; Furthermore, an anti-murine surrogate of SAR445399 alleviates disease and inflammation in an Imiquimod-induced skin inflammation model with superior efficacy than IL-1 blockade alone. In summary, SAR445399 is a broad IL-1 pathway drug hitting 3 birds with 1 stone and is uniquely positioned to potentially raising the efficacy ceiling where a single agent therapy may not be fully efficacious in dermatology or other immunology areas.
- |||||||||| itepekimab (SAR440340) / Sanofi, Regeneron, Dupixent (dupilumab) / Sanofi, Regeneron
Blocking Either the IL-33 or IL-4R? Pathway Attenuates Inflammatory Mediators of Airway Disease (Walter E. Washington Convention Center, Area G, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_6079; Overall, these findings highlight that IL-33 and IL-4/13 are key drivers of airway inflammation and demonstrate that blocking either the IL-33 or IL-4R? pathway results in significant improvement in airway inflammation via distinct and overlapping mechanisms.
- |||||||||| itepekimab (SAR440340) / Sanofi, Regeneron
Interleukin-33 (IL-33) Drives Type 1 and Type 2 Inflammation and Instructs Airway Remodeling (Marriott Marquis Washington, Independence Ballroom Salons A-D (Level M4)) - Mar 25, 2023 - Abstract #ATS2023ATS_4052; Itepekimab binding to IL-33 prevents the formation of IL-33/ST2/IL-1RAcP complex and prevents any IL-33-induced signaling in vitro and in vivo. Using both primary human cells and mouse models, we show here that IL-33 exhibits pleiotropic functions in airway disease, driving both type 1 and type 2 inflammation, as well as lung remodeling.
- |||||||||| Review, Journal: Impact of Biologic Therapy on the Small Airways Asthma Phenotype. (Pubmed Central) - Oct 15, 2022
As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti-alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.
- |||||||||| itepekimab (SAR440340) / Sanofi, Regeneron
Trial completion date, Trial primary completion date: AERIFY-2: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (clinicaltrials.gov) - Sep 1, 2022 P3, N=1170, Recruiting, Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma. Trial completion date: Jul 2024 --> Jan 2025 | Trial primary completion date: Feb 2024 --> Aug 2024
- |||||||||| itepekimab (SAR440340) / Sanofi, Regeneron, Dupixent (dupilumab) / Sanofi, Regeneron
IL-33 and IL-4Rα blockade impact distinct and overlapping inflammatory mediators of airway disease (TP-7 in thematic poster area) - Jun 22, 2022 - Abstract #ERS2022ERS_3785; IL-33 blockade distinctly reduced innate cytokines and ST2+ CD4+ T cells whereas IL-4Rα blockade reduced IgE production, B cell activation and lung chemokines. These findings suggested that blocking either IL-33 or IL-4Ra results in significant improvement in airway inflammation via distinct and overlapping mechanisms.
- |||||||||| Journal: Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma. (Pubmed Central) - Jun 15, 2022
Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores...Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin (TSLP), and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma. This review article aims to pragmatically summarise the latest key clinical data on anti-alarmin therapies in severe asthma and put these findings into context with regards to currently available downstream cytokine blockers.
- |||||||||| Review, Journal: Specific Therapy for T2 Asthma. (Pubmed Central) - Apr 24, 2022
Seemingly under study and promising, are anti-interleukin-33 (itepekimab) and anti-suppressor of tumorigenicity-2 (astegolimab). With this study, we want to provide an overview of these drugs, paying particular attention to their mechanism of action, the main endpoints reached in clinical trials, the main results obtained in real life and some unclear points regarding their usage.
|