B32-52 Efficacy of Tezepelumab Across Multiple Biomarker-Defined Subgroups in Chinese Patients With Severe Uncontrolled Asthma: A Post-Hoc Analysis of the Direction Study

Rationale

Tezepelumab is a human monoclonal antibody that targets thymic stromal lymphopoietin (TSLP), an important regulator acting upstream of multiple inflammatory pathways in asthma. The DIRECTION study assessed the efficacy and safety of tezepelumab in adults with severe uncontrolled asthma. This post-hoc analysis evaluates its efficacy in Chinese patients with various baseline inflammatory biomarker profiles and allergy statuses.

Methods

The DIRECTION study (NCT03927157) is a phase 3, multicenter, double-blind, placebo-controlled trial conducted in Asia. Patients aged 18-80 years with severe uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo every 4 weeks for 52 weeks. The efficacy of tezepelumab in terms of annualized asthma exacerbation rate (AAER) and pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1) were evaluated in the overall Chinese population as well as in subgroups stratified by baseline inflammatory biomarkers (i.e., elevated blood eosinophil [EOS] and elevated fractional exhaled nitric oxide [FeNO]) and patient-reported allergy status.

Results

A total of 308 Chinese patients were included in this analysis, with 155 receiving tezepelumab and 153 receiving placebo. Overall, tezepelumab reduced AAER by 80% over 52 weeks versus placebo (rate ratio [RR]: 0.20, 95% confidence interval [CI]: 0.12, 0.33). Tezepelumab also improved pre-BD FEV1 compared with placebo (least squares mean [LSM] difference at Week 52: 0.28 L, 95% CI: 0.18, 0.38), with a LSM (standard error) change from baseline of + 0.38 (0.035) L. Improvements with tezepelumab treatment versus placebo were observed in AAER and pre-BD FEV1 across all subgroups by inflammatory biomarkers and allergy status (Table 1). Reductions in AAER and improvements in pre-BD FEV1 versus placebo were pronounced in patients having elevated biomarkers with/without allergy. In patients with baseline EOS ≥150 cells/µL, FeNO ≥25 ppb and allergy, RR (95% CI) versus placebo for AAER was 0.14 (0.06, 0.36), and LSM difference (95% CI) versus placebo in pre-BD FEV1 was 0.37 (0.19, 0.55) L. In patients with baseline EOS ≥300 cells/µL, FeNO ≥50 ppb and allergy, RR (95% CI) versus placebo for AAER was 0.02 (0.00, 0.23), and LSM difference (95% CI) versus placebo in pre-BD FEV1 was 0.51 (0.20, 0.82) L.

Conclusion

Tezepelumab reduced asthma exacerbations and improved lung function in Chinese patients with severe uncontrolled asthma. Efficacy was observed regardless of inflammatory biomarker levels and allergy status, with pronounced improvements in patients having elevated biomarkers with/without allergy.

This abstract is funded by: AstraZeneca and Amgen