Advances in type 2-high asthma therapy: what remains missing?

Introduction: Type 2-high asthma (T2HA) accounts for most severe asthma morbidity and is driven by eosinophilic, IgE- and alarmin-mediated inflammation. Although five biologics are licensed, many patients remain symptomatic, corticosteroid-dependent or financially excluded. Areas covered: PubMed, Embase, Web of Science, Scopus, Cochrane Library, EconLit, ClinicalTrials.gov and WHO-ICTRP were searched (1 January 2005–30 June 2025). Evidence from randomized trials, economic evaluations and translational studies on biologics, small-molecule drugs, cell-based and microbiome-directed interventions was synthesized across four domains: late-stage attrition, ultra-long-acting biologic limitations, slow small-molecule progress, and cost–access barriers. Durability, pediatric data and OCS-sparing potential were also examined. Expert opinion: Phenotype-guided biologics have replaced corticosteroid escalation after two decades of research; nevertheless, plateaus in effectiveness, uncertain long-term safety profiles, and exorbitant costs persist. Future progress will depend on value-based pricing that facilitates global adoption, adaptive biomarker-anchored clinical trials, rational combination or bispecific therapeutics, and rigorous post-marketing surveillance of cell-based and microbiome-directed therapies. Delivering sustainable, equitable management of T2HA necessitates the coordination of scientific, regulatory, and economic mechanisms rather than focusing on increasingly narrow cytokine targets.