Monoclonal antibodies (biologicals) are increasingly emerging as targeted therapies that block specific molecular pathways in severe asthma. Monoclonal antibodies work by binding to and blocking the function of a specific target molecule (e.g. anti-IgE or anti-interleukin-5). Monoclonal antibody treatments are also expensive. As such, patient phenotyping and targeted use of biologicals in severe asthma is critical. An individual will only respond to a particular treatment, if that specific molecule / pathway underlies their disease. For more information, see Diagnosis & Assessment – Phenotyping.
Omalizumab (anti-IgE)
Omalizumab (anti-IgE) binds to circulating Immunoglobulin E (IgE) in the blood and tissues. It acts rapidly to block cross-linking of IgE receptors on mast cells and basophils, preventing allergic activation, and gradually down regulates IgE receptor expression on various immune cells. Further details on mechanism of action are available in (Grainge et al. 2016).
Omalizumab is approved for people aged ≥6 years in Australia for the treatment of patients with severe, allergic asthma with specific eligibility and assessment criteria. Omalizumab is indicated for the management of patients with severe allergic asthma, who are already being treated with maximal recommended asthma therapy, and who have serum IgE levels (≥ 30 IU/mL) and evidence of allergic sensitisation as measured by allergy skin tests or serum allergen-specific IgE. Omalizumab treatment reduces exacerbation rates by approximately 45% and hospitalisations by over 80% (Normansell et al. 2014). Further, reductions in ICS and OCS doses have been demonstrated. For more information see Omalizumab Clinic Recommendations.
Mepolizumab (anti-IL-5)
Mepolizumab (anti-IL-5) blocks the binding of Interleukin 5 (IL-5) to its receptor, reducing the production and survival of eosinophils. IL-5 is the major cytokine responsible for the growth, differentiation, recruitment, activation and survival of eosinophils. Further details on mechanism of action are available in (Grainge et al. 2016).
Mepolizumab is approved for people ≥12 years of age in Australia for the treatment of severe eosinophilic asthma. Responding patients are adults and adolescents with severe asthma, who experience persistent asthma exacerbations despite optimal inhaled therapy, and with evidence of eosinophilia from blood eosinophil counts (≥300 cells/μL or ≥0.3 x 109 cells/L) or sputum eosinophilia (>3%) (Gibson et al. 2017). In clinical trials, mepolizumab treatment reduced hospitalisations by ~50% and has been demonstrated to have an oral-steroid sparing effect. For more information see Mepolizumab Clinic Recommendations.
Benralizumab (anti-IL-5 receptor)
Benralizumab (anti-IL-5 receptor) blocks the effect of Interleukin 5 (IL-5) on eosinophils and induces antibody-mediated cell cytotoxicity, causing eosinophil cell death. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation and survival of eosinophils. As a result, eosinophil numbers are reduced following benralizumab exposure. Further details on mechanism of action are available in (Grainge et al. 2016).
Benralizumab is approved for people ≥12 years of age in Australia for the treatment of uncontrolled severe eosinophilic asthma. Responding patients are adults and adolescents with severe asthma, who experience persistent asthma exacerbations despite optimal inhaled therapy, and with evidence of eosinophilia from blood eosinophil counts (≥300 cells/μL or ≥0.3 x 109 cells/L) or sputum eosinophilia (>3%). In clinical trials, benralizumab treatment reduced hospitalisations by ~60% and has been demonstrated to have an oral-steroid sparing effect. For more information see Benralizumab Clinical Recommendations.
Dupilumab (anti- IL-4Rα)
Dupilumab (anti- IL-4Rα) is a recombinant human IgG4 monoclonal antibody that inhibits interleukin-4 and interleukin-13 signaling by binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes. Dupilumab inhibits IL-4 signaling via the Type I receptor (IL4Rα/γc), and both IL-4 and IL-13 signalling through the Type II receptor (IL-4Rα/IL-13Rα).
Dupilumab is approved for people ≥6 years of age in Australia for the treatment of uncontrolled severe eosinophilic asthma or severe allergic asthma. Dupilumab has demonstrated efficacy in reducing annualized exacerbation rates and the rate of severe exacerbations leading to hospitalizations and/or emergency department visits. Additionally, significant increases in pre-bronchodilator FEV1 have been observed in clinical trials evaluating dupilumab. For more information see Dupilumab Clinical Recommendation
Omalizumab, mepolizumab, benralizumab and dupilumab can be can be accessed via application to the PBS. If the application is approved, medication will be provided for 28-32 weeks. This provides clinicians with sufficient time to assess if the monoclonal antibody is effective or not. Patients should be advised that noticeable improvement in their asthma is generally not immediate, and may take a few months to become apparent. The PBS will only approve ongoing treatment if there is clear evidence of improvement.
Comparative studies between omalizumab, mepolizumab, and benralizumab are limited, largely due to the differing indications of these therapies—some targeting allergic asthma and others eosinophilic asthma. There remains a clear need for randomized controlled trials to enable direct comparisons. An analysis of confidence intervals conducted by Lipworth et al. (2025) demonstrated that dupilumab achieved greater overall reductions in annualised exacerbation rates compared to mepolizumab or benralizumab, while tezepelumab was more effective than benralizumab. In patients with eosinophil counts ≥ 300/μL, exacerbation rates were lower with tezepelumab, dupilumab, and mepolizumab relative to benralizumab. Additionally, in patients with eosinophil counts < 150/μL, tezepelumab showed lower exacerbation rates than dupilumab (Lipworth et al. 2025). Note: Tezepelumab is not currently listed on the PBS in Australia.
In some situations, the initiation and continued administration of monoclonal antibodies may be considered in primary care, provided specific conditions are met. This approach may be reasonable where the patient has to travel long distances to the specialist’s clinic or where no ready access to a day procedure unit or outpatient clinic is available. Access recommendations for monoclonal antibody initiation in primary care here.
Monoclonal antibodies currently available in Australia for severe refractory asthma
| Drug name | Target | Asthma phenotype | Availability | Clinical Recommendation |
| Omalizumab | IgE | Allergic asthma | PBS | Click here |
| Mepolizumab | IL-5 | Eosinophilic asthma | PBS | Click here |
| Benralizumab | IL-5 Receptor | Eosinophilic asthma | PBS | Click here |
| Dupilumab | Common IL-4/IL-13 Receptor | Eosinophilic/Allergic asthma | PBS | Click here |
Monoclonal antibodies and other novel targeted therapies under development for severe refractory asthma
| Drug name | Molecular target | Asthma phenotype |
| Ligelizumab | IgE | Allergic asthma |
| Reslizumab | IL-5 | Eosinophilic asthma |
| Fevipiprant | Prostaglandin D2 receptor | Allergic asthma |
| Lebrikuzumab | IL-13 | ‘Type 2 high’ asthma |
| Tralokinumab | IL-13 | ‘Type 2 high’ asthma |
| Tezepelumab | Thymic stromal lymphopoietin (TSLP) | Seems to be effective, regardless of eosinophilia |
(Tezepelumab has been approved by the TGA in Australia. However, there is no release date for when it will be available in the PBS)
Additional Resources:
- Inflammation Biomarkers in the Assessment and Management of Severe Asthma – Tools and Interpretation: This document provides an overview of fractional exhaled nitric oxide (FeNO) and eosinophil numbers as biomarkers to inform asthma management, including assessment approaches and interpretation of findings.
