Depemokimab demonstrates efficacy in patients with type 2 asthma with comorbid CRSwNP: Phase III SWIFT-1/-2 analysis

Introduction: The efficacy of twice-yearly depemokimab was demonstrated in the Phase III SWIFT-1/-2 trials for type 2 asthma characterized by blood eosinophils, and ANCHOR-1/-2 trials for chronic rhinosinusitis with nasal polyps (CRSwNP). Up to 40% of patients with severe asthma are estimated to have comorbid CRSwNP, an overlap associated with increased disease burden. Depemokimab may therefore offer meaningful clinical benefit in this subpopulation. This analysis evaluated the efficacy of depemokimab in patients with type 2 asthma and comorbid CRSwNP using pooled data from SWIFT-1/-2. Methods: Patients with type 2 asthma were randomized 2:1 to receive depemokimab 100 mg subcutaneously or placebo, plus standard of care, every 26 weeks for 52 weeks. Pre-specified outcomes included annualized exacerbation rates over 52 weeks, and St George's Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores over 52 weeks, analyzed by baseline comorbid CRSwNP subgroup. Results: = 33], with a rate ratio (95% CI) of 0.31 (0.17, 0.58). Additionally, an improvement in least squares (LS) mean SGRQ total score in the depemokimab group vs. placebo was noted after 4 weeks of treatment [-7.12-point difference (95% CI: -13.41, -0.83)] which was sustained up to 52 weeks [-8.32-point difference (95% CI: -15.77, -0.88)] in the asthma with CRSwNP subgroup. Similarly, an improvement from baseline in LS mean ACQ-5 score was noted with depemokimab vs. placebo after 2 weeks of treatment [-0.40-point difference (95% CI: -0.79, -0.01)], which was maintained up to 52 weeks [-0.76-point difference at (95% CI: -1.23, -0.28)] in the asthma with CRSwNP subgroup. Discussion: Twice-yearly depemokimab reduced annualized exacerbation rates and demonstrated greater improvements in SGRQ and ACQ-5 scores vs. placebo in patients with type 2 asthma and comorbid CRSwNP. These improvements were greater than those reported in the overall SWIFT-1/-2 population. These findings identify that type 2 asthma with CRSwNP is a clinically recognizable phenotype that is likely to have enhanced benefit with depemokimab therapy. Clinical trial identifiers: NCT04719832/NCT04718103.