Investigational agents targeting alarmins for asthma treatment: insights and progress from phase I and II trials

Asthma is a chronic and heterogeneous airway disease in which epithelial-derived cytokines - TSLP, IL-33, and IL-25-act as upstream drivers of inflammation. Over the past decade, these alarmin cytokines have become key therapeutic targets, leading to the development of a new generation of biologics designed to intervene early in the inflammatory cascade.

This review discusses findings from Phase I and II clinical trials investigating anti-alarmin therapies, including monoclonal antibodies and novel delivery platforms targeting TSLP, IL-33, and IL-25. A comprehensive literature search was conducted across PubMed, ClinicalTrials.gov, and recent conference proceedings to summarize safety, pharmacokinetic, and efficacy outcomes, as well as emerging biomarkers and genetic insights related to treatment response.

Early-phase studies confirm that alarmin blockade is safe, biologically relevant, and efficacious for improving airway inflammation across multiple asthma phenotypes. TSLP inhibition is an approved and clinically available therapy, while IL-33 and IL-25 remain in earlier development. Future progress will rely on optimized airway-focused dosing strategies such as biomarker-guided patient selection and genetic profiling, to achieve optimal personalized therapy. Anti-alarmin biologics are poised to redefine asthma management by addressing inflammation at the epithelial origin of common asthma triggers and advancing clinical care toward precision medicine.