BACKGROUND Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals. METHODS In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care. The primary end point was the annualized rate of exacerbations at 52 weeks. Secondary end points, which were analyzed in a hierarchical manner to adjust for multiplicity, included the change from baseline in the score on the St. George's Respiratory Questionnaire (SGRQ), the forced expiratory volume in 1 second, and asthma symptom reports at 52 weeks. RESULTS Across the two trials, 792 patients underwent randomization and 762 were included in the full analysis; 502 were assigned to receive depemokimab and 260 to receive placebo. 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 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. No significant between-group difference in the change from baseline in the SGRQ score was observed in either trial, so no statistical inference was drawn on subsequent secondary end points. The proportion of patients with any adverse event was similar in the two groups in both trials. CONCLUSIONS Depemokimab reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype. (Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.).

中文翻译：

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每年两次 Depemokimab 治疗具有嗜酸性粒细胞表型的严重哮喘。


背景 Depemokimab 是一种超长效生物疗法，对白细胞介素 5 的结合亲和力增强，可实现有效的 6 个月给药间隔。方法 在这些 3A 期、随机、安慰剂对照重复试验中，我们评估了 depemokimab 在严重哮喘和嗜酸性粒细胞表型患者中的疗效和安全性，其特征是嗜酸性粒细胞计数高（过去 12 个月每微升 ≥300 个细胞或筛选时每微升 ≥150 个细胞）和尽管接受了中等或高剂量吸入糖皮质激素，但仍有恶化史。患者以 2：1 的比例随机分配，在第 0 周和第 26 周接受 depemokimab（皮下注射剂量为 100 mg）或安慰剂，以及标准治疗。主要终点是 52 周时的年化恶化率。次要终点以分层方式分析以调整多重性，包括 St. George's 呼吸问卷 （SGRQ） 评分相对于基线的变化、1 秒用力呼气量和 52 周时的哮喘症状报告。结果 在两项试验中，792 名患者接受了随机分组，762 名患者被纳入完整分析;502 例接受 Depemokimab，260 例接受安慰剂。地培莫单抗组的年化恶化率为 0.46 （95% 置信区间 [CI]），0.36 至 0.58），安慰剂组为 1.11 （95% CI，0.86 至 1.43） （率比，0.42;95% CI，0.30 至 0.59;P<0.001） 和 0.56 （95% CI，0.44 至 0.70） 和安慰剂组 1.08 （95% CI，0.83 至 1.41） （率比，0.52;95% CI，0.36 至 0.73;P<0.001） 在 SWIFT-2 中。 在两项试验中，均未观察到 SGRQ 评分相对于基线变化的组间显著差异，因此未对后续次要终点进行统计推断。在两项试验中，两组发生任何不良事件的患者比例相似。结论 Depemokimab 降低了嗜酸性粒细胞表型重症哮喘患者的年化恶化率。（由 GSK 资助;SWIFT-1 和 SWIFT-2 ClinicalTrials.gov 编号 NCT04719832 和 NCT04718103。