Depemokimab Reduces Exacerbations Regardless of Baseline Asthma Control

A twice-yearly biologic appears to significantly reduce asthma exacerbations, even in patients whose asthma was under control at baseline.

Investigators found that most patients who received the ultra–long-acting interleukin-5-targeting antibody depemokimab experienced clinically meaningful responses after 52 weeks.¹ The study was published in the American Journal of Respiratory and Critical Care Medicine.

Depemokimab significantly reduces asthma exacerbations, benefiting patients regardless of their baseline asthma control levels.

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The new results were part of a post hoc subgroup analysis of pooled data from the SWIFT-1/2 studies of depemokimab. The new analysis was designed to compare outcomes based on Asthma Control Questionnaire-5 (ACQ-5) scores at baseline.

Previous phase 3A data showed that depemokimab led to a significant reduction in the annualized rate of exacerbations compared to placebo in a cohort of nearly 800 patients with an eosinophilic phenotype of asthma who continued to have exacerbations despite the use of medium- or high-dose inhaled glucocorticoids.²

Those earlier trials were open to patients regardless of ACQ-5 scores and thus included patients with and without uncontrolled asthma. The new study stratified patients to examine patient outcomes based on whether they had an ACQ-5 score below 1.5 or at or above 1.5. The latter group would qualify as having uncontrolled asthma symptoms.

The analysis included patients ages 12 and older who used medium- to high-dose corticosteroids, had at least 2 exacerbations in the past year, and had a blood eosinophil count of at least 150 cells/µL at screening or ≥ 300 cells/µL any time in the year before the trial’s initiation. Those patients were randomized on a 2:1 basis to receive either depemokimab or placebo every 26 weeks. The primary endpoint was change in annualized exacerbation rate at 52 weeks. Secondary endpoints included change in St. George’s Respiratory Questionnaire (SGRQ) score and change in ACQ-5 score. The majority of the 744 patients included in the analysis had ACQ-5 scores above 1.5 at baseline (75%), while one-quarter of patients had scores below 1.5 at baseline.

The investigators found that the annualized exacerbation rate for the controlled asthma group fell by 53% after a year. It fell by 54% for the uncontrolled asthma group. Among those with uncontrolled asthma, 69% were classified as responders to therapy based on improvement in SGRQ score, compared to 63% among the patients treated with placebo. Those in the controlled-asthma group had an SGRQ-based response rate of 51%, compared to 55% in the placebo group. There was a trend toward improvement in ACQ-5 scores compared to placebo in the uncontrolled asthma group, first author I.D. Pavord, DM, of the University of Oxford, and colleagues wrote.

The investigators noted that it was significant that the benefits in exacerbation reduction were similar notwithstanding the patient’s baseline ACQ-5 score.

“Twice-yearly depemokimab consistently reduced exacerbations versus placebo regardless of baseline asthma control, suggesting uncontrolled asthma symptoms are not required to experience an exacerbation reduction in patients with a history of exacerbations,” they wrote.

In March, depemokimab’s developer, GSK, announced the FDA had accepted for review a biologics license application for depemokimab in 2 indications, including asthma with type 2 inflammation.³ The application has a Prescription Drug User Fee Act date of December 16. If eventually approved by the agency, the drug would become the first ultra–long-lasting biologic with 6-month dosing to be approved by the agency, the company said.

References

1. Pavord ID, Chupp GL, Jackson DJ, et al. Twice-yearly depemokimab reduces exacerbations and improves quality of life in patients with uncontrolled asthma symptoms at baseline: subgroup analyses of the phase III SWIFT-1/2 studies. Am J Respir Crit Care Med. 2025;211:A5234. doi:10.1164/ajrccm.2025.211.Abstracts.A5234
2. Jackson DJ, Wechsler ME, Jackson DJ, et al. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N Engl J Med. 2024;391(24):2337-2349. doi:10.1056/NEJMoa2406673
3. Depemokimab applications accepted for review by the US FDA for asthma with type 2 inflammation and for chronic rhinosinusitis with nasal polyps (CRSwNP). News release. GSK. Published March 3, 2025. Accessed June 18, 2025. https://www.gsk.com/en-gb/media/press-releases/depemokimab-applications-accepted-for-review-by-the-us-fda/