What are the biologic treatments for asthma?

From the Guidelines

Biologic treatments for asthma, such as omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, are recommended for patients with severe, uncontrolled asthma who do not respond adequately to standard therapies, as they can significantly reduce exacerbations, improve lung function, reduce oral corticosteroid use, and enhance quality of life. These biologics target specific inflammatory pathways involved in asthma pathophysiology, including IgE, IL-5, IL-4, IL-13, and TSLP. The most recent and highest quality study 1 supports the use of biologics in severe asthma, with omalizumab being a potential therapeutic approach for patients with allergic asthma. Key points to consider when selecting a biologic treatment for asthma include:

• Evaluating specific inflammatory markers, such as IgE and eosinophil counts, to determine the most appropriate biologic
• Assessing treatment response after 4-6 months and continuing therapy if beneficial
• Considering the potential risks and benefits of each biologic, including the risk of anaphylaxis with omalizumab 1
• Monitoring liver function and serum concentrations of certain medications, such as zileuton and theophylline 1 Some of the biologics used for asthma treatment include:
• Omalizumab (Xolair), which blocks IgE and is administered at 150-375mg subcutaneously every 2-4 weeks for allergic asthma
• Mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra), which target IL-5 or its receptor to reduce eosinophilic inflammation
• Dupilumab (Dupixent), which blocks IL-4 and IL-13 signaling and is administered as 200-300mg subcutaneously every 2 weeks for eosinophilic or oral corticosteroid-dependent asthma
• Tezepelumab (Tezspire), which targets TSLP and is given as 210mg subcutaneously every 4 weeks for severe asthma regardless of inflammatory phenotype. Overall, biologic treatments offer a promising approach for managing severe, uncontrolled asthma, and selection of the most appropriate biologic should be based on individual patient characteristics and inflammatory markers 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

1. 1 Mechanism of Action Asthma, Chronic Rhinosinusitis with Nasal Polyps, and IgE-Mediated Food Allergy Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and dendritic cells, resulting in FcεRI down-regulation on these cells In allergic asthmatics, treatment with omalizumab inhibits IgE-mediated inflammation, as evidenced by reduced blood and tissue eosinophils and reduced inflammatory mediators, including IL-4, IL-5, and IL-13.

14 CLINICAL STUDIES

1. 1 Clinical Studies in Patients with Asthma The efficacy of FASENRA for the add-on maintenance treatment of severe asthma, and with an eosinophilic phenotype was evaluated in two randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials, SIROCCO (NCT01928771) and CALIMA (NCT01914757), for 48 and 56 weeks in duration, respectively

Biologic treatments for asthma include:

• Omalizumab (SQ): inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and dendritic cells, resulting in FcεRI down-regulation on these cells 2
• Benralizumab (SQ): add-on maintenance treatment for severe asthma with an eosinophilic phenotype, evaluated in two randomized, double-blind, parallel-group, placebo-controlled, exacerbation trials, SIROCCO and CALIMA 3 3 Key points:
• Omalizumab inhibits IgE-mediated inflammation
• Benralizumab is used for add-on maintenance treatment of severe asthma with an eosinophilic phenotype
• Both treatments have been evaluated in clinical trials and have shown efficacy in reducing asthma exacerbations and improving lung function

From the Research

Biologic Treatments for Asthma

• Biologic therapies have revolutionized the management of severe asthma by reducing exacerbations, improving lung function, and enhancing patient quality of life 4, 5, 6, 7.
• Several biologics are available, including omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab, which target different pathways, such as IgE, IL-5, and IL-4 4, 5, 6, 7.
• These biologics have been shown to be effective in reducing exacerbations, improving lung function, and reducing oral corticosteroid requirements in patients with severe asthma 4, 5, 6, 7.

Mechanism of Action

• Omalizumab is an anti-IgE monoclonal antibody that is licensed for severe allergic asthma and has been shown to decrease exacerbations by augmenting deficient antiviral immune responses in asthma 4.
• Mepolizumab, reslizumab, and benralizumab target the IL-5-eosinophil pathway and have been shown to reduce exacerbation rates in patients with raised blood eosinophil counts 4, 5, 6, 7.
• Dupilumab targets the IL-4 receptor and has been shown to be effective in reducing exacerbation rates, oral corticosteroid requirements, and improving lung function 4, 5, 6.

Clinical Efficacy and Safety

• Clinical efficacy of biologics is greatest in patients with elevated T2 biomarkers, such as peripheral blood eosinophils and exhaled nitric oxide 4, 5, 6, 7.
• Biologics have been shown to have excellent safety profiles, with no major safety concerns raised in clinical trials 4, 5, 6, 7.
• Real-life studies have demonstrated the effectiveness of biologics, such as benralizumab, mepolizumab, and omalizumab, in improving asthma and nasal outcomes in patients with severe allergic asthma associated with nasal polyps 8.

Patient Selection and Treatment

• Patient selection for biologic therapy is based on individual characteristics, such as rate of exacerbations, use of systemic corticosteroids, and presence of comorbidities 4, 5, 6, 7.
• Biomarkers, such as peripheral blood eosinophils and exhaled nitric oxide, can help predict response to certain biologics 4, 5, 6, 7.
• Emerging biologics and small molecule antagonists are being developed to target other pathways of airway inflammation, including T2 low or non-T2 asthma 6.