Depemokimab, an ultra-long-acting IL-5-targeted monoclonal antibody, reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype, according to a report on the SWIFT studies.1
Key findings
SWIFT-1 and SWIFT-2 were phase 3A, randomized, placebo-controlled replicate trials that compared the safety and efficacy of depemokimab with placebo in patients with severe asthma and an eosinophilic phenotype, characterized by high blood eosinophil counts (BECs; ≥ 300 cells/µL in the previous 12 months or ≥ 150 cells/µL at screening) and a history of exacerbations despite receiving medium- or high-dose inhaled glucocorticoids.
The primary end point, the annualized rate of exacerbations, was met; depemokimab significantly reduced exacerbation rates in both studies. In SWIFT-1, the exacerbation rate was 0.46 with depemokimab vs 1.11 with placebo (rate ratio of 0.42); and in SWIFT-2, the exacerbation rate was 0.56 with depemokimab vs 1.08 with placebo (rate ratio of 0.52; P < .001) for both. There were similar adverse effects in both groups.
Data in context
IL-5, the target of depemokimab, plays a key role in the maturation, activation, proliferation, migration, and survival of eosinophils. Eosinophils, in turn, orchestrate airway type 2 inflammation and asthma pathogenesis.
Therapeutic advances in asthma and related conditions have been propelled by an improved understanding of type 2 inflammation. Chief among these advances is the approval of biologic therapies that reduce asthma exacerbations.
Two IL-5-directed monoclonal antibodies, mepolizumab and reslizumab, are approved for treating patients with severe asthma and an eosinophilic phenotype.
Lauren E. Eggert, MD, Clinical Assistant Professor of Medicine at Stanford University, framed the SWIFT results, saying, “Depemokimab is similar to the IL-5-targeted drug mepolizumab that was approved by the [US Food and Drug Administration (FDA)] for asthma in 2015; although, depemokimab was designed to have higher target affinity.”
She noted that the same population of patients with severe asthma, with BECs of ≥ 150 cells/µL at screening or ≥ 300 cells/µL in the previous 12 months, appeared to benefit from depemokimab and mepolizumab.
“These data are significant because the class of drugs that depemokimab belongs to, IL-5 blockers, is one that asthma clinicians are familiar with and have been using for a decade or so,” Dr. Eggert said. “We now have this new option that is an ultra-long-acting, high-affinity IL-5 inhibitor that needs to be dosed only once every six months.”
Both mepolizumab and reslizumab are administered once every four weeks.
Implications of SWIFT
Many patients with severe uncontrolled asthma may qualify for more than one biologic. Currently, there are no head-to-head trials comparing different biologics. Treatment choice may be informed by several factors, including availability/access, steroid-sparing efficacy, and patient-related factors.
A key patient-related factor that can dictate choice of therapy is the dosing frequency.
“As a clinician, the dosing scheme is exciting because, until now, my patients with asthma and related conditions are often initiated on biologics dosed every two weeks or monthly,” Dr. Eggert said. “Also, one of the first questions that my patients ask is, ‘How long am I going to have to be on this therapy?’ Having a biologic that requires only twice-yearly dosing would be a nice option for patients.”
She identified two patient populations where she envisions depemokimab fitting into her practice.
“The first would be patients for whom I would otherwise be considering an IL-5 agent,” she said. “Depemokimab would be another option that I would offer this patient. Another group of patients would be those who are already on, and doing well on, an IL-5 agent like mepolizumab. The consideration would be whether the patient wants to switch to the twice-yearly dosing option with depemokimab for convenience.” This medication may be especially suitable for individuals with poor treatment adherence or those who rely on nursing visits for biologic injections.
Dr. Eggert noted that the SWIFT studies did not find statistically significant differences in the St. George’s Respiratory questionnaire, a secondary outcome, or in symptom improvement between depemokimab and placebo.
Looking ahead
Dr. Eggert called attention to a post hoc analysis of the SWIFT studies, presented at the 2025 American Thoracic Society International Conference, which showed that depemokimab reduced exacerbations, regardless of baseline asthma control, compared with placebo.
Dr. Eggert noted that the SWIFT trial population was not restricted to patients with uncontrolled symptomatic asthma at baseline. Indeed, the subgroup analysis, with patients stratified by baseline Asthma Control Questionnaire-5 (ACQ-5) scores, showed a trend toward greater ACQ-5 improvement in patients with uncontrolled asthma symptoms at baseline who were treated with depemokimab.
Based on the SWIFT data, the FDA has accepted a Biologics License Application for depemokimab in patients with severe asthma with an eosinophilic phenotype, with a Prescription Drug User Fee Act date of December 16, 2025.
Dr. Eggert said depemokimab could be a “great new option for both patients and providers” if approved.
References
1. 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
