Tezepelumab reduces exacerbations, improves lung function, QoL in severe, uncontrolled asthma

Treatment with the human monoclonal antibody tezepelumab reduced exacerbations and improved asthma control, lung function, and quality of life in adults and adolescents with severe, uncontrolled asthma, according to the phase III NAVIGATOR study presented as a poster at AAAAI 2021.

Participants in this multicentre, double-blind trial were 1,059 non-smoking individuals aged 12–80 years (mean age 49.5 years, 36.5 percent male, 27.9 percent Asian) with severe, uncontrolled asthma treated with medium- or high-dose inhaled corticosteroids for ≥12 months pre-screening (24.8 and 75.1 percent, respectively) and ≥1 additional controller medication with or without oral corticosteroids for ≥3 months before informed consent date.

They were randomized 1:1 to receive subcutaneous tezepelumab (210 mg; n=528) or placebo (n=531) Q4W for 52 weeks. The patients were required to have ≥2 asthma exacerbations warranting systemic corticosteroid treatment or hospitalization 12 months before informed consent date.

About 9 percent of patients were on oral corticosteroids and 40 percent had experienced >2 exacerbations in the previous year. Baseline mean blood eosinophil count and fractional exhaled nitric oxide (FeNO) level were 340 cells/μL and 43.8 ppb, respectively, mean serum total IgE was 565 IU/mL, and mean prebronchodilator forced expiratory volume in 1 second (FEV₁) was 1.8 L.

Over the 52-week period, there was a significant 56 percent reduction (95 percent confidence interval [CI], 47–63; p<0.001) in annualized asthma exacerbation rate (AAER) among patients assigned to tezepelumab compared with placebo in the overall population (rate ratio [RR], 0.44, 95 percent CI, 0.37–0.53). [AAAAI 2021, abstract L46]

When assessed according to baseline blood eosinophil count, there was a significant 41 percent (95 percent CI, 25–54; p<0.001) reduction in AAER with tezepelumab vs placebo among patients with a blood eosinophil count of <300 cells/μL at baseline (RR, 0.59, 95 percent CI, 0.46–0.75).

Although nonsignificant, AAER was reduced by 70, 39, and 61 percent over the 52-week period with tezepelumab vs placebo in patients with baseline blood eosinophil counts of ≥300, <150, and ≥150 cells/μL, respectively. The AAER reductions with tezepelumab vs placebo were consistent regardless of FeNO level and allergic status at baseline, though the reductions appeared more marked among patients with blood eosinophil counts of ≥300 cells/μL (RR, 0.30 vs 0.59 for <300 cells/μL) and FeNO ≥25 ppb (RR, 0.32 vs 0.68 for <25 ppb) at baseline. There was also a 79 percent reduction in exacerbation-associated hospitalization or emergency department visit with tezepelumab vs placebo.

At week 52, there was a greater improvement from baseline in prebronchodilator FEV₁ with tezepelumab than placebo (least squares [LS] mean change, 0.23 vs 0.10 L; difference, 0.13 L, 95 percent CI, 0.08–0.18; p<0.001).

“[These] improvements were observed from the first post-baseline assessment (week 2) and were sustained throughout the treatment period,” said the authors.

There was also a greater improvement from baseline to week 52 in Asthma Control Questionnaire-6 (ACQ-6) score in the tezepelumab compared with the placebo group (LS mean change, -1.53 vs -1.20; difference, -0.33, 95 percent CI, -0.46 to -0.20; p<0.001) as well as in Asthma Quality of Life Questionnaire (standardized) for patients aged 12 years and older (AQLQ[S]+12) score (LS mean change, 1.48 vs 1.14; difference, 0.33, 95 percent CI, 0.20–0.47; p<0.001). There was also a greater improvement in Asthma Symptom Diary (ASD) overall score between baseline and week 52 with tezepelumab vs placebo (LS mean change, -0.70 vs -0.59; difference, -0.11, 95 percent CI, -0.19 to -0.04; p=0.004).

“Safety findings were similar between tezepelumab and placebo groups,” said the authors. Adverse events (AEs) were reported in 77.1 and 79.5 percent of patients in the tezepelumab and placebo groups, respectively, and serious AEs in 8.7 and 13.2 percent, respectively. The most frequently (≥3 percent of patients) reported events were nasopharyngitis, upper respiratory tract infection, and headache. There were no reports of treatment-related anaphylactic reactions or Guillain-Barré syndrome.

“These are ground-breaking results for the many patients with severe asthma who continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics,” said lead investigator Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital, London, UK. [https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-is-the-first-biologic-to-consistently-and-significantly-reduce-exacerbations-in-broad-population-of-severe-asthma-patients.html, accessed 25 March 2021]

“Tezepelumab has the potential to transform treatment for a broad population of patients with severe asthma regardless of their type of inflammation, including those with and without an eosinophilic phenotype,” he added.