What are the clinical trials supporting all the biologic medications for asthma, including medications such as Omalizumab (Anti-IgE), Mepolizumab (Interleukin-5 (IL-5) inhibitor), Reslizumab (IL-5 inhibitor), Benralizumab (Interleukin-5 receptor alpha (IL-5Rα) inhibitor), and Dupilumab (Interleukin-4 receptor alpha (IL-4Rα) inhibitor)?

From the Guidelines

Several biologic medications have been approved for the treatment of severe asthma based on clinical trial evidence, including Omalizumab, Mepolizumab, Reslizumab, Benralizumab, Dupilumab, and Tezepelumab, which target different pathways in asthma pathophysiology and provide options for patients with specific inflammatory profiles who remain symptomatic despite standard treatments. The clinical trials supporting these biologics include:

• Omalizumab (Xolair), which was supported by the INNOVATE, EXTRA, and SOLAR trials, demonstrating efficacy in allergic asthma by reducing exacerbations and improving quality of life 1
• Mepolizumab (Nucala), which was validated through the DREAM, MENSA, and SIRIUS trials, showing benefits in eosinophilic asthma with reduced exacerbations and steroid-sparing effects 1
• Reslizumab (Cinqair), which was approved based on the BREATH program studies, demonstrating improved lung function and reduced exacerbations in patients with elevated eosinophils 1
• Benralizumab (Fasenra), which was supported by the SIROCCO, CALIMA, and ZONDA trials, showing efficacy in reducing exacerbations and oral corticosteroid use through its unique eosinophil-depleting mechanism 1
• Dupilumab (Dupixent), which was approved following the LIBERTY ASTHMA QUEST and VENTURE trials, demonstrating effectiveness in both eosinophilic and type 2 inflammatory asthma with improvements in lung function and reduced exacerbations 1
• Tezepelumab (Tezspire), which was most recently approved based on the PATHWAY and NAVIGATOR trials, showing efficacy across different asthma phenotypes by targeting thymic stromal lymphopoietin 1 These biologics have been shown to improve outcomes in patients with severe asthma, including reducing exacerbations, improving lung function, and reducing oral corticosteroid use. Some key points to consider when selecting a biologic for asthma treatment include:
• The patient's specific inflammatory profile and asthma phenotype
• The presence of comorbidities, such as atopic dermatitis or nasal polyposis
• The patient's history of response to previous treatments, including corticosteroids and other biologics
• The potential benefits and risks of each biologic, including efficacy, safety, and cost.

From the FDA Drug Label

Across three clinical trials (SIROCCO, CALIMA, and ZONDA) for asthma, 1,808 patients received at least 1 dose of FASENRA [see Clinical Studies (14. 1)]. The data described below reflect exposure to FASENRA in 1,663 patients, including 1,556 exposed for at least 24 weeks and 1,387 exposed for at least 48 weeks The safety exposure for FASENRA is derived from two Phase 3 placebo-controlled trials (SIROCCO and CALIMA) from 48 weeks duration [FASENRA every 4 weeks (n=841), FASENRA every 4 weeks for 3 doses, then every 8 weeks (n=822), and placebo (n=847)] Following subcutaneous administration of mepolizumab 100 mg every 4 weeks for 32 weeks in adult and adolescent subjects with severe asthma (Trial 2), blood eosinophils were reduced to a geometric mean count of 40 cells/mcL, which corresponds to a geometric mean reduction of 84% compared with placebo The pharmacodynamic response (blood eosinophil reduction) was also evaluated in children aged 6 to 11 years with severe asthma. Following subcutaneous administration of mepolizumab 40 mg every 4 weeks for 52 weeks, blood eosinophils were reduced to a geometric mean count of 48 cells/mcL.

The clinical trials supporting mepolizumab and benralizumab for asthma are:

• Mepolizumab: Trial 1, Trial 2
• Benralizumab: SIROCCO, CALIMA, ZONDA, TATE 2 3 3

From the Research

Asthma Biologics Clinical Trials

The following asthma biologics have been supported by clinical trials:

• Benralizumab: reduces exacerbation rates with high certainty of evidence, incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72) 4
• Dupilumab: reduces exacerbation rates with high certainty of evidence, IRR 0.43 (95% CI 0.32 to 0.59) 4
• Mepolizumab: reduces exacerbation rates with high certainty of evidence, IRR 0.49 (95% CI 0.38 to 0.66) 4
• Omalizumab: reduces exacerbation rates with high certainty of evidence, IRR 0.56 (95% CI 0.40 to 0.77) 4
• Reslizumab: reduces exacerbation rates with high certainty of evidence, IRR 0.46 (95% CI 0.37 to 0.58) 4

Real-World Effectiveness and Switching Biologics

Real-world studies have confirmed the effectiveness of asthma biologics in reducing exacerbations, improving lung function, and quality of life 5, 6

• A retrospective study found that biologic therapy was associated with a 59% reduction in clinically significant exacerbations and a 54% reduction in maintenance oral corticosteroid dose 5
• Patients who were previously on another biologic also experienced significant improvements in exacerbation frequency, maintenance oral corticosteroid dose, and asthma control 5

Comparing Trial Designs and Study Results

Clinical trials for asthma biologics have varying inclusion criteria, study designs, and endpoints, making it challenging to compare results 7

• A review of major phase II and phase III clinical trials for FDA-approved asthma biologics found that baseline clinical traits and severity of study populations differed significantly 7
• Understanding the details and differences in asthma biologic trial designs, patient cohorts, and study results can help guide care providers in choosing the most appropriate biologic for patients 7