The Exchange

Commentary and Observations from
the Medical Front Lines

A New Biologic on the Horizon for Severe Asthma

A New Biologic on the Horizon for Severe Asthma

There are currently 5 available monoclonal antibody treatments for patients with moderate to severe asthma, all of which target immunoglobulin E (IgE) or type 2 inflammatory cytokines involved in eosinophilic inflammation. While the currently available biologic therapies (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab) have been extremely effective for many asthmatics, there are still many patients with non-eosinophilic or non-allergic asthma who do not have an adequate response to these medications.

A phase III trial was recently completed showing efficacy of tezepelumab, a new monoclonal antibody that targets thymic stromal lymphopoietin (TSLP). TSLP is a cytokine involved in airway obstruction and oral corticosteroid resistance in severe asthmatics. TSLP is thought to be involved in other inflammatory pathways outside of type 2 inflammation and therefore may be effective for non-eosinophilic and non-allergic asthma.

The phase III, multicenter, randomized, double-blind, placebo-controlled trial evaluated the effectiveness of tezepelumab vs placebo in reducing annualized asthma exacerbation rates in adolescents and adults. Secondary endpoints included evaluation of improvement in lung function (forced expiratory volume in one second [FEV1]), asthma control scores, and asthma-related quality of life scores.

Overall, 1061 patients aged 12 to 80 years were enrolled. The annualized asthma exacerbation rate in the tezepelumab group was 0.93 compared with 2.10 in the placebo group. In patients who had low eosinophil counts—typically regarded as an eosinophil count of less than 300 cells per microliter—the asthma exacerbation rate over 52 weeks was 1.02 in the tezepelumab group vs 1.73 in the placebo group. Significant improvements in asthma symptom scores, control scores, and asthma-related quality of life were also seen in the tezepelumab group, as well as improvement in pre-bronchodilator FEV1 (0.23 liters vs 0.09 liters in placebo group). Furthermore, the annualized rate of exacerbations that resulted in hospitalization or emergency department visits was 0.06 with tezepelumab and 0.28 in the placebo-treated participants.

Through the course of the study period, 2.1% in the tezepelumab group withdrew from the study due to adverse events, compared with 3.6% in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, and asthma (which was observed more frequently in the placebo group). Injection site reactions were more common in the tezepelumab group (3.6%) than in the placebo group (2.6%), although no treatment-related anaphylactic reactions were reported.

Overall, tezepelumab was shown to significantly reduce exacerbations in adults and adolescents with severe, uncontrolled asthma. Improvement was also seen in patients with low blood eosinophil counts. Tezepelumab was shown to be safe and well-tolerated, and it may prove to be a viable treatment option in the future for patients who are not candidates for, or have not responded to, currently available biologic therapies for asthma.

  • Menzies-Gow A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. NEJM. 2021;384:1800.

Filed under: Allergy/Immunology, Pulmonary Medicine

Development Widget