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WASHINGTON -- Patients with severe, uncontrolled asthma taking tezepelumab (Tezspire) reported significantly improved cough and phlegm production, compared with patients taking placebo, in a secondary analysis of the phase III NAVIGATOR trial.

In a separate post-hoc analysis of the trial data, no significant sex-related differences in response to the thymic stromal lymphopoietin (TSLP)-targeting biologic were observed, with males and females showing similar responses in key measures of asthma control.

Both analyses were presented in a poster session at the annual meeting of the American Thoracic Society.

Mario Castro, MD, of Washington University School of Medicine in St. Louis, told MedPage Today that the TSLP-blocking activity of tezepelumab, which reduces airway inflammation and hyper-responsiveness, is the likely driver of the cough and phlegm reductions reported by NAVIGATOR participants taking the drug.

The multicenter study included adolescent and adult patients with severe, uncontrolled asthma despite being on daily medium- or high-dose inhaled corticosteroids for a year or more prior to enrollment, along with an additional controller drug, with or without oral corticosteroids.

Patients were randomized 1:1 to treatment with subcutaneous tezepelumab 210 mg (n=528) or subcutaneous placebo (n=531) every 4 weeks for 52 weeks, with baseline clinical characteristics and demographics similar between the two groups.

Patients reporting higher frequent productive cough had higher blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels, and frequent productive cough and blood eosinophil counts of ≥300 cells/µL at baseline were associated with poorer lung function.

Improved Cough and Phlegm Production

At baseline, mean St. George's Respiratory Questionnaire (SGRQ) scores for patient-reported cough and phlegm production were similar among the 433 tezepelumab recipients and 430 placebo recipients included in the post-hoc analysis (2.97 vs 2.93, respectively, for cough and 2.53 vs 2.50 for phlegm production).

Approximately 41% of patients in both study arms who completed the SGRQ met the criteria for frequent productive cough at study enrollment.

At week 52, more tezepelumab than placebo recipients did not have frequent productive cough (82.1% vs 70.2%, odds ratio 2.01, 95% CI 1.47-2.75).

In patients with baseline frequent productive cough, greater reductions in cough and phlegm were observed at week 52 with tezepelumab than with placebo across the blood eosinophil count and FeNO subgroups.

Outcomes by Sex

The post-hoc analysis examining tezepelumab response in NAVIGATOR by sex was presented by Monica Kraft, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

Kraft told MedPage Today that sex differences in asthma prevalence and severity are well known, with women more likely than men to be diagnosed with asthma, and more likely to have severe disease.

"Tezepelumab reduced exacerbations, while improving lung function, asthma control, and health-related quality of life compared with placebo, to similar degrees in male and female participants over 52 weeks," she said. "These results further support the efficacy of tezepelumab in a broad population of patients with severe uncontrolled asthma."

Of the 1,059 patients enrolled in NAVIGATOR, 36.5% were male and 63.5% were female.

Baseline demographics and clinical characteristics were similar between the male and female subgroups, and baseline mean (standard deviation) forced expiratory volume in 1 second (FEV₁) was higher in male (2.2 [0.8] L) than in female (1.6 [0.6] L) patients.

A higher proportion of male patients were sensitized to at least one perennial aeroallergen (69.3% vs 61.3%), and more males had nasal polyps (19.1% vs 13.5%).

Asthma exacerbation rates over 52 weeks of treatment with tezepelumab were similar (55% in males, 57% in females).

In the placebo group, however, asthma exacerbation rates over 52 weeks were higher in female (2.35, 95% CI 2.00-2.75) compared with male (1.69, 95% CI 1.36-2.09) patients.

Improvements from baseline to week 52 in pre-bronchodilator FEV₁ with tezepelumab compared with placebo were numerically greater in male patients (least-squares [LS] mean difference 0.19 L, 95% CI 0.11-0.28) than in female patients (LS mean difference 0.10 L, 95% CI 0.04-0.16).

Improvements in percent predicted pre-bronchodilator FEV₁ with tezepelumab compared with placebo, however, were similar between male patients (LS mean difference 5.60%, 95% CI 2.96-8.25) and female patients (LS mean difference 4.35%, 95% CI 2.35-6.35).