New Biologic Significantly Reduces Asthma Exacerbations Requiring Hospitalization
The new biologic therapy tezepelumab significantly reduced exacerbations requiring hospital stays and emergency department (ED) visits for adults and adolescents with severe, uncontrolled asthma.
Tezepelumab is a human monoclonal antibody designed to block the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in asthma pathogenesis. Thymic stromal lymphopoietin can cause severe pathologic airway inflammation and, ultimately, structural changes in the airways. Patients with severe asthma are at an increased risk of mortality and, compared with patients with persistent asthma, have twice the risk of asthma-related hospitalizations.
“Tezepelumab offers new therapeutic opportunities for patients who are currently ineligible for biologic treatments. It may also challenge the current mandatory step of biomarker assessment before initiating a biologic,” said Arnaud Bourdin, MD, professor, Département de Pneumologie et Addictologie, PhyMedExp, University of Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France. He said the investigational drug is the first and only asthma biologic to consistently demonstrate in randomized trials clinically meaningful exacerbation reductions irrespective of key biomarkers, including blood eosinophil counts (EOS), allergic status, and fractional exhaled nitric oxide.
The phase 3 randomized, placebo-controlled, double-blind, multicenter NAVIGATOR study evaluated the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. The study enrolled patients, age 12 to 80 years, with severe, uncontrolled asthma who were being treated with medium- or high-dose inhaled corticosteroids and at least one other asthma controller medication. The 1,061 patients were randomly assigned to receive tezepelumab 210 mg subcutaneously (529 patients) or placebo (532 patients) every 4 weeks for 52 weeks.
The study results were published simultaneously in the New England Journal of Medicine.
The investigators estimated the annualized rate of asthma exacerbations that required hospitalization or an ED visit for the two groups over 52 weeks, and assessed the time to first evaluation that required hospitalization or ED visit. They also evaluated the proportion of patients who required asthma-related healthcare resources over the 52 weeks.
Results show tezepelumab demonstrated significant and clinically meaningful reductions in annualized asthma exacerbation rates (AAER) across all eosinophil level subgroups: 70% AAER reduction in EOS≥300; 41% AAER reduction in EOS <300; and 39% AAER reduction in EOS <150. Tezepelumab also reduced the rate of exacerbations that required hospitalization or an emergency room visit by 79%, as compared with placebo. The investigational therapy prolonged the time to first exacerbation that required hospitalization or an ED visit, as compared with placebo, with a risk reduction of 65%.
A lower proportion of patients in the tezepelumab group than in the placebo group required asthma-related hospitalizations (3.2% vs. 7%), ED visits (4.4% vs. 9.4%), unscheduled visits to a specialist (35.4% vs. 43.5%), telephone calls with a healthcare provider (19.1% vs. 25%), or ambulance transport (0.8% vs. 2.3%). In addition, tezepelumab demonstrated statistically significant improvements in key secondary endpoints compared with placebo in lung function, asthma control, and health-related quality of life.
The researchers observed improvements in tezepelumab-treated patients as early as the second week of treatment or at the first time-point assessment. These improvements were sustained throughout the treatment period, said Bourdin.
In conclusion, Bourdin said, “These results show that tezepelumab has the potential not only to treat a broad population of severe asthma patients, but also to reduce the burden severe asthma places on healthcare systems. Once on the market, this therapy presents the real possibility that severe asthma patients will no longer have to be hospitalized.”
Arnaud Bourdin, MD
Financial relationships with relevant companies within the past 24 months:
Actelion – consultancy fee, investigator/co-investigator for clinical trials
AstraZeneca – grants, consultancy fees, investigator/co-investigator for clinical trials
Boehringer Ingelheim - grants, consultancy fees, investigator/co-investigator for clinical trials
Cephalon/Teva – grants
Chiesi - consultancy fees, investigator/co-investigator for clinical trials
Galapagos - investigator/co-investigator for clinical trials
GlaxoSmithKline - grants, consultancy fees, investigator/co-investigator for clinical trials
MedinCell – consultancy fees
Merck - consultancy fees, investigator/co-investigator for clinical trials
Novartis - grants, consultancy fees, investigator/co-investigator for clinical trials
Roche - consultancy fees, investigator/co-investigator for clinical trials
Sanofi-Regeneron - grants, consultancy fees, investigator/co-investigator for clinical trials
Vertex - investigator/co-investigator for clinical trials