Early and Sustained Efficacy of Depemokimab in Type 2 Asthma: A Pooled Analysis of the SWIFT-1/-2 Studies

BACKGROUND:Depemokimab, the first ultra-long-acting biologic with enhanced IL-5 binding affinity, high inhibition potency, and extended half-life, enables twice-yearly dosing in patients with asthma. In phase III SWIFT-1/-2 trials, depemokimab significantly reduced the annualized exacerbation rate by 54% versus placebo with sustained suppression of inflammation assessed by blood eosinophil count in type 2 asthma. OBJECTIVE:To evaluate the onset and duration of depemokimab efficacy across each 26-week dosing period in the pooled SWIFT-1/-2 population and identify patient characteristics associated with enhanced clinical response. METHODS:Patients with type 2 asthma, independent of Asthma Control Questionnaire-5 (ACQ-5) status, were randomized 2:1 to receive depemokimab 100 mg subcutaneously or placebo every 26 weeks for 52 weeks. Prespecified end points included time to first exacerbation, St George's Respiratory Questionnaire total score, ACQ-5 score, Asthma Nighttime Symptom Diary weekly score, Asthma Daytime Symptom Diary weekly score, and rescue medication use over time. We conducted post hoc subgroup analyses by baseline characteristics. RESULTS:Depemokimab reduced the probability of first exacerbation over 52 weeks versus placebo by 46% (hazard ratio = 0.54; 95% CI, 0.43-0.69), with effects from week 4 sustained across both dosing periods. Annualized exacerbation rate reductions were most pronounced in patients with asthma disease duration less than 10 years, comorbid chronic rhinosinusitis with nasal polyps, and medium-dose inhaled corticosteroids (ICS) at baseline. Across each dosing period, depemokimab also improved St George's Respiratory Questionnaire, ACQ-5, Asthma Nighttime Symptom Diary, and Asthma Daytime Symptom Diary scores, particularly in patients with baseline ACQ-5 scores of 1.5 or greater, with sustained improvements in rescue medication. CONCLUSION:Early and sustained efficacy with depemokimab was observed across 26-week dosing periods in type 2 asthma, with enhanced benefits in patients with shorter disease duration who had not progressed to high-dose ICS.