Late Breaking Abstract - DESTINATION: tezepelumab long-term safety and efficacy versus placebo in patients with severe, uncontrolled asthma

Abstract

Background: Tezepelumab reduced the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma in the phase 3 NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) studies.

Objective: To assess the safety and efficacy of tezepelumab (210 mg every 4 weeks) over 2 years.

Methods: DESTINATION was a phase 3, multicentre, randomized, placebo-controlled, double-blind, extension study (NCT03706079) of patients (12–80 years old) who completed NAVIGATOR or SOURCE. Patients previously randomized to tezepelumab continued treatment. Those previously randomized to placebo were re-randomized 1:1 to placebo or tezepelumab. Exposure-adjusted incidence rates (patients with event/total exposure) of adverse events (AEs) and serious AEs (SAEs) (primary endpoints), AAER (secondary endpoint) and biomarker (blood eosinophils, FeNO and IgE) levels were assessed over 104 weeks in patients who received ≥1 dose of tezepelumab or placebo in the parent studies.

Results: In patients who initially received tezepelumab (n=528) or placebo (n=531) in NAVIGATOR, incidence rates per 100 patient years were 49.62 and 62.66 for AEs and 7.85 and 12.45 for SAEs, respectively, over 104 weeks. In those who initially received tezepelumab (n=74) or placebo (n=76) in SOURCE, incidence rates were 47.15 and 69.97 for AEs and 13.14 and 17.99 for SAEs, respectively. Tezepelumab reduced the AAER over 104 weeks versus placebo by 58% (95% CI: 49–65) and 39% (95% CI: 4–62) in NAVIGATOR and SOURCE patients, respectively, and reduced biomarker levels versus placebo.

Conclusion: Tezepelumab was well tolerated for up to 2 years and resulted in clinically meaningful reductions in asthma exacerbations.