Novel asthma treatments: Advancing Beyond Approved Novel Step-Up Therapies for Asthma

Over the past two decades, the management of severe asthma has shifted from relying on inhaled corticosteroids and bronchodilators to more precise, targeted approaches. Monoclonal antibodies (mAbs) designed to address specific molecular pathways in asthma have transformed care for patients with severe asthma. Since therapy targeting immunoglobulin E (IgE) became the first biologic developed for allergic asthma in 2003, monoclonal antibodies targeting interleukin (IL)-5, IL-5 receptor, IL-4/13 receptor, and thymic stromal lymphopoietin (TSLP) have been approved for treating difficult-to-treat asthma, improving symptoms, reducing exacerbations, and reducing oral corticosteroid dosing. Despite these advances, many patients continue to experience asthma exacerbations and symptoms, and fail to achieve remission. To address this, pharmaceutical companies and researchers are exploring novel therapies targeting different aspects of asthma pathophysiology, including cytokines, enzymes, and cellular pathways. Innovative treatments like inhaled biologics, ultra-long-acting biologics, and combination biologics are in development. New molecular targets, such as Bruton tyrosine kinase (BTK), Ox40 ligand, and Janus kinase (JAK), offer promise for addressing unmet needs in asthma care. While many therapies have failed to get approval for use due to lack of efficacy, trial design, or toxicity, these experiments still provide insights into asthma's underlying mechanisms. The future of asthma management looks promising, with emerging therapies aiming to improve patient outcomes. The challenge will lie in identifying the right therapy for each patient and developing personalized treatment strategies.