Biologic Therapies for Asthma: A Comprehensive Guide to Targeted Treatments

Asthma is a chronic respiratory condition affecting millions worldwide, and while traditional therapies like inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) remain foundational, many patients with severe asthma continue to experience uncontrolled symptoms. In recent years, biologic therapies have emerged as transformative options for individuals with specific asthma phenotypes. These targeted treatments work by interrupting key pathways in the immune system that drive inflammation, particularly in type 2 (T2) high asthma. This article explores the major classes of biologics currently approved or under investigation, their mechanisms of action, clinical benefits, and considerations for use across different patient populations.

Anti-IgE Therapy: Omalizumab

Omalizumab, a recombinant humanized IgG1 monoclonal antibody, targets immunoglobulin E (IgE), a central player in allergic asthma. It is administered via subcutaneous injection every 2–4 weeks and is indicated for patients with moderate-to-severe allergic asthma who are sensitized to at least one perennial aeroallergen and have elevated serum IgE levels (typically >30 IU/mL). The dosing regimen is carefully calculated based on both body weight and baseline total IgE concentration.

By binding to the constant region of free IgE, omalizumab prevents IgE from attaching to high-affinity receptors (FcεRI) on mast cells, basophils, and dendritic cells. This interruption reduces the release of inflammatory mediators that trigger bronchoconstriction and airway hyperresponsiveness.

Clinical trials in children with severe asthma have demonstrated significant reductions in asthma exacerbations and hospitalizations. Long-term treatment over 12 months has been associated with improved lung function, better asthma control, and enhanced quality of life. Notably, studies show that omalizumab can reduce reliance on oral corticosteroids, making it a valuable option for steroid-sparing strategies.

One intriguing finding is the benefit of initiating omalizumab 4–6 weeks before the school year—a period historically linked to increased asthma flare-ups due to viral infections and allergen exposure. This preventive approach has proven especially effective in pediatric patients requiring Step 5 therapy according to global asthma guidelines.

Targeting IL-5 Pathway: Eosinophil-Driven Asthma

Eosinophilic inflammation is a hallmark of a subset of severe asthma characterized by elevated blood and sputum eosinophils. Interleukin-5 (IL-5) plays a pivotal role in the maturation, recruitment, activation, and survival of eosinophils in the bone marrow and airways. Three biologics—mepolizumab, reslizumab, and benralizumab—have been developed to disrupt this pathway, offering new hope for patients with severe eosinophilic asthma.

Mepolizumab: Blocking IL-5 Directly

Mepolizumab is a humanized monoclonal antibody that binds directly to IL-5, preventing its interaction with the IL-5 receptor on eosinophils. Approved for patients aged 12 years and older, mepolizumab significantly reduces annual asthma exacerbation rates by nearly 50% in clinical trials.

In addition to reducing flare-ups, mepolizumab improves lung function—as measured by pre-bronchodilator FEV1—and enhances asthma control and health-related quality of life. Importantly, no increase in serious adverse events has been observed; in fact, some data suggest a reduction, likely due to fewer asthma-related complications.

The recommended dose is 100 mg administered subcutaneously every four weeks. Patient eligibility typically includes an absolute blood eosinophil count of ≥150 cells/μL at initiation or ≥300 cells/μL within the prior 12 months.

Reslizumab: Intravenous Option for Adults

Reslizumab is another anti-IL-5 monoclonal antibody, but unlike mepolizumab, it is given intravenously. It is approved for adults aged 18 and older with severe eosinophilic asthma and a peripheral eosinophil count of at least 400 cells/μL.

The standard regimen is 3 mg/kg infused every four weeks. Studies involving patients aged 12–75 have shown clinically meaningful reductions in exacerbation frequency, improvements in FEV1, and better quality of life compared to placebo. Safety profiles are favorable, with no significant difference in serious adverse events between reslizumab and control groups.

Due to its IV administration, reslizumab requires clinic visits for infusion, which may impact patient convenience but ensures adherence.

Benralizumab: Targeting the IL-5 Receptor

Benralizumab stands out by targeting the alpha subunit of the IL-5 receptor (IL-5Rα), expressed on eosinophils and basophils. Beyond blocking IL-5 signaling, benralizumab induces antibody-dependent cell-mediated cytotoxicity (ADCC), leading to direct depletion of eosinophils.

Phase 3 randomized, double-blind, placebo-controlled trials (RDBPCTs) have shown that benralizumab significantly reduces asthma exacerbations and improves symptom control in adolescents and adults (12–75 years) with severe, uncontrolled asthma despite high-dose ICS and LABA therapy. Health-related quality of life also showed marked improvement.

The most common side effects include worsening asthma, upper respiratory tract infections, and nasopharyngitis—all generally mild to moderate. The dosing schedule involves three initial 30 mg subcutaneous injections every four weeks, followed by maintenance doses every eight weeks.

Dual Inhibition of IL-4 and IL-13: Dupilumab

Dupilumab represents a broader approach by inhibiting shared signaling of two key type 2 cytokines: IL-4 and IL-13. It does so by binding to the IL-4 receptor alpha (IL-4Rα), thereby blocking downstream signaling critical for Th2 inflammation, mucus production, and airway remodeling.

In clinical trials involving patients aged 12 and older with uncontrolled moderate-to-severe asthma, dupilumab significantly reduced severe exacerbations and improved FEV1 (P < 0.001). In corticosteroid-dependent patients, it enabled substantial reductions in oral steroid use while maintaining asthma control and further decreasing exacerbation rates.

FDA-approved as an add-on maintenance therapy for patients with eosinophilic phenotype or oral corticosteroid dependence, dupilumab is administered subcutaneously with an initial loading dose of 400–600 mg, followed by 200–300 mg every other week.

Emerging Biologics in Development

While current biologics focus primarily on IgE, IL-5, and IL-4/IL-13 pathways, next-generation therapies aim to target upstream initiators of inflammation.

Fevipiprant: A CRTh2 Antagonist

Fevipiprant is an oral antagonist of the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2), which binds prostaglandin D2 (PGD2). PGD2-CRTh2 interaction recruits and activates ILC2s and Th2 cells, promoting the release of IL-4, IL-5, and IL-13.

Phase 3 trials showed fevipiprant improved FEV1, enhanced asthma control, and reduced sputum eosinophil counts—particularly in patients with high T2 biomarkers. Although development was discontinued for strategic reasons, it highlighted the potential of targeting early inflammatory triggers.

Tezepelumab: Targeting TSLP

Tezepelumab is a novel monoclonal antibody that neutralizes thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine acting as a master switch in airway inflammation. TSLP activates dendritic cells, mast cells, ILC2s, and eosinophils, amplifying the entire Th2 cascade.

In a Phase 3 trial, tezepelumab significantly reduced annualized exacerbation rates and improved pre-bronchodilator FEV1 in adults with severe asthma, regardless of baseline eosinophil levels. This broad efficacy suggests potential utility even in non-eosinophilic or low-T2 phenotypes.

Currently approved for adults and adolescents (12+), tezepelumab offers a promising option for patients who don't qualify for other biologics due to lower biomarker levels.

Non-Biologic Intervention: Bronchial Thermoplasty

Beyond pharmacologic therapies, bronchial thermoplasty offers a procedural alternative for adults with severe persistent asthma inadequately controlled by ICS and LABAs. This bronchoscopic procedure delivers controlled radiofrequency energy to the airway walls, reducing the mass of smooth muscle responsible for excessive bronchoconstriction.

Approved by the FDA for adults, bronchial thermoplasty has been shown to improve quality of life and reduce emergency department visits and missed work or school days. However, it carries a higher risk of post-procedure adverse events, including hospitalization, and comes with significant cost implications.

Long-term outcomes remain uncertain, and current evidence is limited to adult populations. Due to lack of safety and efficacy data, it is not recommended for children or adolescents.

Conclusion and Future Outlook

The era of precision medicine in asthma management is well underway. Biologic therapies have revolutionized care for patients with severe, difficult-to-treat asthma by targeting specific inflammatory pathways. From omalizumab in allergic asthma to dupilumab and tezepelumab in broader T2 inflammation, these agents offer improved symptom control, reduced exacerbations, and steroid-sparing benefits.

As research continues, future therapies may expand beyond current targets, offering hope for patients with non-type 2 asthma and younger populations. Personalized treatment plans based on biomarkers such as IgE, eosinophils, FeNO, and periostin will become increasingly vital in optimizing outcomes and transforming asthma from a burdensome disease into a manageable condition.