About the Trials
SWIFT-1
- Trial Name: Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-1)
- ClinicalTrials.gov ID: NCT04719832
- Sponsor: GlaxoSmithKline
- Completion Date: November 21, 2023
SWIFT-2
- Trial Name: A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-2)
- ClinicalTrials.gov ID: NCT04718103
- Sponsor: GlaxoSmithKline
- Completion Date: April 11, 2024
A recent study found that depemokimab (GSK3511294; GSK) was successful in reducing the annualized rate of exacerbations in patients with severe asthma with an eosinophilic phenotype. The ultra-long-acting biologic therapy has an enhanced binding affinity for interleukin (IL)-5 and may enable effective 6-month dosing intervals.1
Previously, the study authors noted that depemokimab demonstrated an acceptable safety profile in adult patients with mild or moderate asthma and a blood eosinophil count of at least 200 cells per microliter during a single-dose phase 1 study. Additionally, depemokimab led to the suppression of the blood eosinophil count that was sustained over the study’s 26-week duration.1
The authors initiated SWIFT-1 (NCT04719832)2 and SWIFT-2 (NCT04718103)3, 2 randomized, placebo-controlled, replicate phase 3a trials to evaluate the safety and efficacy of depemokimab in patients 12 years and older with severe asthma and an eosinophilic phenotype that is characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) who had a history of exacerbations despite receiving medium- or high-dose inhaled glucocorticoids.1
For both trials, patients were randomly assigned to receive either 100 mg of adjuvant depemokimab or placebo, both of which were administered subcutaneously via a pre-filled syringe once every 26 weeks (weeks 0 and 26). Additionally, patients were maintained on their existing baseline maintenance asthma standard of care treatment throughout the studies’ durations.2,3
The primary outcome measure for both studies was annualized rate of clinically significant exacerbations up to 52 weeks. Secondary outcome measures included changes from baseline in St. George Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores, as well as pre-bronchodilator forced expiratory volume in 1 second (FEV1) and annualized rate of hospitalization and/or emergency department (ED) visits because of asthma-related exacerbations. Additionally, the frequency and severity of adverse events (AEs) were also assessed.2,3
Across the 2 studies, a total of 792 patients with severe asthma were enrolled and randomly assigned. Of these patients, 762 were included in the full analysis (SWIFT-1: N = 382; SWIFT-2: N = 380). Across the studies, 502 patients received depemokimab compared with 260 who received placebo. Patients who were treated with depemokimab experienced a lower annualized rate of exacerbations at the 52-week point, with patients in SWIFT-01 and SWIFT-02 having rates of about 0.46 (95% CI, 0.36-0.58) and 0.56 (95% CI, 0.44-0.70), respectively. Additionally, the rates for placebo were about 1.11 (95% CI, 0.86 to 1.43) and 1.08 (95% CI, 0.83 to 1.41).1
According to the investigators, patients in SWIFT-1 demonstrated a mean change from baseline in SGRQ score of -13.03 (95% CI, -15.22 to -10.84) and -9.67 (95% CI, -12.71 to -6.64) in the depemokimab and placebo groups, respectively. Mean changes in SWIFT-2 were about -14.80 (95% CI, -16.85 to -12.75) and -12.49 (95% CI, -15.36 to -9.63), respectively. Overall, there were no significant between-group differences in the change from baseline in SGRQ scores in either trial, therefore, no statistical inference was drawn on subsequent secondary end points.1
In the SWIFT-1 trial, asthma exacerbations occurred in approximately 32% (81 patients, 124 events) of patients in the depemokimab group and 46% (61 patients, 151 events in the placebo group. The rates of exacerbations were similar to their respective groups in the SWIFT-2 trial (depemokimab: 32%, 81 patients, 159 events; placebo: 50%, 64 patients; 167 events).1
Further, the proportion of patients reporting any AE was similar in the depemokimab and placebo groups in SWIFT-1 (73% in both groups) and SWIFT-2 (depemokimab: 72%; placebo: 78%). The study investigators noted that there were no serious AEs that were found to be related to either depemokimab or placebo.1
In SWIFT-1, there was a greater proportion of patients in the depemokimab group that had an AE that was categorized as influenza, whereas in SWIFT-2, the proportion of patients with influenza was higher in the placebo group. None of these occurrences were considered by the investigators to be related to either depemokimab or placebo. Nasopharyngitis was also reported by patients in both studies (SWIFT-1: 12% in depemokimab and 19% in placebo; SWIFT-2: 13% in depemokimab and 21% in placebo). Regarding laboratory and electrocardiogram results, there were no meaningful differences between the 2 groups.1
REFERENCES
1. Jackson DJ, Wchsler ME, Bernstein D, et al. Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. N Engl J Med. 2024;391:2337-234. doi:10.1056/NEJMoa2406673
2. Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-1). ClincialTrials.gov identifier: NCT04719832. Updated December 17, 2024. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT04719832
3. A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-2). ClinicalTrials.gov identifier: NCT04718103. Updated November 29, 2024. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT04718103
