An analysis of the phase 3 NAVIGATOR trial shows tezepelumab did not provide differing efficacy among men and women, despite historic trends of disparate severe asthma outcomes among sexes.
Biologic tezepelumab provides similar clinical benefit to both men and women with severe, uncontrolled asthma, according to new findings from an assessment of the phase 3 pivotal NAVIGATOR study.1
In new analyses presented at the American Thoracic Society (ATS) 2023 International Conference in Washington, DC, this week, a team of AstraZeneca-supported investigators reported that tezepelumab was associated with overall improved lung function and disease control among adults with severe asthma regardless of their sex. The findings are promising for prescribers as to how they relate the well-understood sex-based disparity of severe asthma impact in patients.
Led by Monica Kraft, MD, system chair of medicine at Mount Sinai Health System, investigators conducted the pre-specified analysis of NAVIGATOR to interpret tezepelumab’s efficacy in patients based on sex.
A thymic stromal lymphopoietin (TSLP) inhibitor, tezepelumab was approved by the US Food and Drug Administration (FDA) as a self-administered injected pen for the treatment of severe asthma in patients ≥12 years old this February.2 The multicenter, randomized, double-blind, placebo-controlled NAVIGATOR trial assessed a 210 mg subcutaneous dose of tezepelumab administered every 4 weeks, plus standard of care, in 528 patients with severe uncontrolled asthma versus control in 531 patients.
The original findings showed tezepelumab was associated with significantly reduced exacerbations, as well as improved lung function, asthma control and symptoms, and health-related quality of life versus placebo. However, the question of potential patient outcome disparity by sex persisted.
“Asthma is more prevalent and more severe in women than in men, which may be due to variations in genetics and epigenetics, immune responses, hormones, and environmental and sociocultural factors,” Kraft and colleagues wrote.
The team sought a primary end point of annualized asthma exacerbation rate (AAER) among NAVIGATOR patients grouped by sex over 52 weeks. They additionally observed changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1), percent predicted pre-bronchodilator FEV1, Asthma Control Questionnaire-6 (ACQ-6) score and Asthma Quality of Life Questionnaire (AQLQ) for patients ≥12 years old.
Just one-third (36.5%) of the 1059 NAVIGATOR patients were male; 193 were receiving tezepelumab, versus 194 receiving placebo. Another 335 females were receiving tezepelumab, versus 337 receiving placebo. Baseline patient demograpghics and clinical statuses were consistent across male and female patients, though investigators did not a higher mean pre-bronchodilator FEV1 score among males (2.2 L) than females (1.6 L).
Regarding AAER, similar mean reductions over 52 weeks were reported for male patients (55%; 95% CI, 37 - 67) and female patients (57%; 95% CI, 45 – 66) treated with tezepelumab. Investigators observed a greater AAER score in women receiving placebo at 52 weeks than men.
Tezepelumab additionally benefitted pre-bronchodilator FEV1 more significantly than placebo in male patients (mean difference, 5.6%; 95% CI, 2.96 – 8.25) and female patients (mean difference, 4.35%; 95% CI, 2.35 – 6.35) over 52 weeks.
Male and female patients receiving tezepelumab additionally reported similar improvements in ACQ-6 score versus placebo at 52 weeks (-0.34% and -0.32% percent differences). AQLQ among patients ≥12 years old was also similarly improved in male (0.31% difference) and female (0.35% difference) patients receiving tezepelumab at 52 weeks.
The team concluded that the NAVIGATOR analysis showed tezeplumab’s similar impact on lung function, asthma control and health-related quality of life among patients with severe, uncontrolled asthma regardless of their sex.
“These results further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma,” they wrote.