Tezepelumab, marketed under the trade name Tezspire, is a biologic medication designed to treat severe, uncontrolled asthma in patients who have not found sufficient relief with conventional treatments. Severe asthma is a persistent and often debilitating form of the disease that continues to cause frequent symptoms and exacerbations despite the use of high-dose inhaled corticosteroids and other controller medications. This treatment option targets a fundamental pathway of inflammation in the airways, offering a new approach for managing a complex chronic condition.
How Tezepelumab Works in Asthma
Tezepelumab functions as a fully human monoclonal antibody that specifically targets a protein called Thymic Stromal Lymphopoietin (TSLP). TSLP is an epithelial cytokine, meaning it is released by the cells lining the airways in response to triggers like viruses, allergens, or pollutants. This release of TSLP acts as an early, upstream signal in the inflammatory cascade that drives asthma.
By binding to TSLP, tezepelumab prevents this cytokine from interacting with its receptor on immune cells, essentially blocking the inflammatory response at its initiation point. This upstream blockade is what distinguishes tezepelumab from other biologics, which typically target specific, downstream inflammatory mediators like Interleukin-5 (IL-5) or Immunoglobulin E (IgE). Inhibiting TSLP reduces the activation of multiple inflammatory pathways, including those associated with Type 2 inflammation.
The broad effect of TSLP inhibition leads to a reduction in several downstream biomarkers, such as blood eosinophils, IgE, fractional exhaled nitric oxide (FeNO), IL-5, and IL-13. This mechanism provides a comprehensive anti-inflammatory effect, making the treatment effective across a wider range of asthma phenotypes.
Who Qualifies for This Treatment
Tezepelumab is indicated as an add-on maintenance treatment for adults and adolescents aged 12 years and older who have severe asthma. Patients qualify for this therapy if their asthma remains uncontrolled despite being on standard, guideline-recommended therapy. This standard typically involves the use of high-dose inhaled corticosteroids combined with a long-acting beta-agonist.
The treatment is administered as a 210 mg subcutaneous injection every four weeks. Each dose is typically given by a healthcare professional in a clinic or doctor’s office, though a pre-filled pen may be available for self-administration after appropriate training.
This medication is a maintenance therapy and is not intended for the rapid relief of acute asthma symptoms or severe exacerbations. Patients must continue their existing asthma medications, and any reduction in other treatments, particularly oral corticosteroids, should only occur gradually and under medical supervision. Its approval is notable because it does not require patients to have a specific biomarker profile, such as a high eosinophil count.
Measuring Effectiveness in Clinical Trials
The efficacy of tezepelumab was evaluated in major clinical trials, including the Phase 3 NAVIGATOR trial and the Phase 2b PATHWAY trial. The primary measure of effectiveness focused on the reduction of the annualized asthma exacerbation rate (AAER) over a 52-week period. Tezepelumab demonstrated a clinically meaningful reduction in the annual rate of asthma flare-ups compared to placebo.
A pooled analysis of the PATHWAY and NAVIGATOR data showed that tezepelumab reduced the AAER by 60% compared to placebo in patients with severe, uncontrolled asthma. This reduction was consistently observed across various patient subgroups, regardless of their baseline blood eosinophil counts or fractional exhaled nitric oxide (FeNO) levels. For example, in patients with low baseline eosinophil counts (less than 150 cells per microliter), the treatment still provided a meaningful reduction in exacerbations.
Tezepelumab also showed positive results on secondary measures, including improvements in lung function. Patients treated with the biologic experienced improvements in their forced expiratory volume in one second (FEV1) compared to the placebo group. Furthermore, the therapy demonstrated a substantial benefit in reducing exacerbations that led to hospitalization or an emergency department visit.
For patients who relied on maintenance oral corticosteroids (OCS), tezepelumab allowed a greater proportion of them to reduce or discontinue their OCS dose compared to those receiving placebo. The consistent efficacy across different inflammatory phenotypes supports the drug’s upstream mechanism of action.
Safety Profile and Potential Side Effects
The safety profile of tezepelumab has been found to be comparable to that of a placebo in clinical trials. The most frequently reported adverse reactions in patients receiving the treatment included pharyngitis, arthralgia, and back pain. Pharyngitis, which is inflammation of the throat, was a common event reported in the trials.
Healthcare providers advise patients about the potential for hypersensitivity reactions, such as rash or allergic conjunctivitis, which may occur hours or even days after an injection. Patients should be monitored for signs of a serious allergic reaction, and the medication should be stopped immediately if one occurs. Before starting treatment, it is recommended that patients are up-to-date on all necessary immunizations, and live attenuated vaccines should be avoided while on the therapy.