Depemokimab therapy reduces exacerbations in patients with severe eosinophilic asthma

1. In this randomized, placebo-controlled replicate trial, depemokimab decreased the annual rate of exacerbations among patients with severe eosinophilic asthma.

2. Depemokimab had an acceptable safety profile, with rates of adverse effects similar to that of placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Asthma that is inadequately controlled can result in severe exacerbations. Patients who experience frequent exacerbations often have a high level of unregulated inflammation, resulting in high levels of classic T2 cytokines and interleukin 4, 5, and 13. Interleukin-5 is responsible for the growth, recruitment, and activation of eosinophils. Uncontrolled eosinophilic inflammation is a risk factor for asthma exacerbations, airway remodeling, and decline in lung function. Previous proof of concept trials have shown that an anti-interleukin 5 antibody can reduce the frequency of exacerbations in patients with a history of eosinophilic asthma exacerbations. Depemokimab is an ultra-long-acting biologic therapy that has enhanced binding affinity for interleukin-5. SWIFT-1 and SWIFT-2 were phase 3A, randomized, placebo-controlled replicate trials that evaluated the safety and efficacy of depemokimab in patients with severe eosinophilic asthma, characterized by a high eosinophil count and a history of exacerbations despite inhaled glucocorticoid therapy. Patients who met inclusion criteria were randomly assigned in a 2:1 ratio to receive either depemokimab or placebo at weeks 0 and 26, plus standard of care. The primary endpoint for this study was the annualized rate of exacerbations at 52 weeks. Secondary endpoints included changes in score on the St George’s Respiratory Questionnaire, forced expiratory volume in 1 second, and asthma symptoms at 52 weeks. Results from this study found that depemokimab reduced the annualized rate of exacerbations in patients with eosinophilic asthma.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: SWIFT-1 and SWIFT-2 were phase 3A randomized, placebo-controlled replicate trials that investigated the safety and efficacy of depemokimab in patients with severe eosinophilic asthma. Patients who were at least 12 years old, had an asthma diagnosis by a physician at least two years prior, a blood eosinophil count of at least 300 cells/microlitre in the past 12 months or 150 cells/microlitre at screening with inhaled glucocorticoids, current treatment with at least one additional controller for at least three months, and a history of at least two exacerbations requiring systemic glucocorticoids in the past 12 months were eligible for this trial. A total of 792 patients were randomized in a 2:1 ratio to receive either depemokimab at a dose of 100 mg subcutaneously (n=502) or placebo (n=260) at weeks 0 and 26, plus standard of care. The primary endpoint that was evaluated was the annualized rate of exacerbations in 52 weeks, as defined by worsening asthma that required systemic glucocorticoids, hospitalization, or an emergency department visit. A total of 762 patients were included in the full analysis of the results, which found that the annualized rate of exacerbations was 0.46 (95% Confidence Interval [CI], 0.36 to 0.58) with depemokimab and 1.11 (95% CI, 0.86 to 1.43) with the placebo (rate ratio, 0.42; 95% CI, 0.30 to 0.59; p<0.001) in SWIFT-1 and 0.56 (95% CI, 0.44 to 0.70) with depemokimab and 1.08 (95% CI, 0.83 to 1.41) with placebo (rate ratio, 0.52; 95% CI, 0.36 to 0.73; P<0.001) in SWIFT-2. These studies also found that the proportion of patients with adverse events was similar in the treatment and placebo groups. Overall, the results from these studies found that depemokimab had an acceptable safety profile and administration every 6 months resulted in reduced annualized rates of exacerbations among patients with severe eosinophilic asthma.

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