Phase III SWIFT Trials Show Ultra-Long-Acting Biologic Depemokimab Reduces Severe Asthma Exacerbations

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The results of the SWIFT-1 (NCT04719832) and SWIFT-2 (NCT04718103) trials demonstrated that depemokimab administered every six months significantly lowered annual asthma exacerbations in patients with severe eosinophilic asthma, while also maintaining an acceptable safety profile.^1-3 Depemokimab, an anti–interleukin (IL)-5 therapy, is the first ultra-long-acting biologic to be evaluated in Phase III trials that shows a binding affinity and high potency for IL-5.⁴

“Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5, which potentially enables effective 6-month dosing intervals for patients with asthma,” the study authors wrote. “In a single-dose phase 1 study, researchers found that depemokimab had an acceptable safety profile in adult patients with mild or moderate asthma and a blood eosinophil count of at least 200 cells per microliter at screening and led to dose-dependent suppression of the blood eosinophil count that was sustained over a 26-week period.”¹

Trial Design

Both SWIFT-1 and SWIFT-2 are Phase IIIA, randomized, placebo-controlled replicate trials. Investigators analyzed the efficacy and safety of depemokimab among a patient population with severe asthma and an eosinophilic phenotype characterized by high eosinophil count and history of exacerbations following unsuccessful treatment with medium- or high-dose inhaled glucocorticoids.

Investigators randomly assigned 792 patients in a 2:1 ratio to receive either depemokimab administered subcutaneously at a dose of 100 mg or placebo at weeks zero and 26, along with standard care. A total of 762 patients were included in the full analysis, with 502 patients randomly assigned to the depemokimab cohort and 260 patients to the placebo cohort. The trial’s primary endpoint was annualized rate of exacerbations at 52 weeks, with secondary endpoints that included change from baseline in St. George’s Respiratory Questionnaire (SGRQ) score, forced expiratory volume in one second, and asthma symptom reports at 52 weeks.

Trial Results

In the SWIFT-1 trial, the annualized rate of exacerbations was 0.46 (95% confidence interval [CI]), 0.36 to 0.58) in the depemokimab cohort compared to 1.11 (95% CI, 0.86 to 1.43) in the placebo cohort (rate ratio, 0.42; 95% CI, 0.30 to 0.59; P<0.001). In the SWIFT-2 trial, the annualized rate of exacerbations was 0.56 (95% CI, 0.44 to 0.70) in the depemokimab cohort compared to 1.08 (95% CI, 0.83 to 1.41) in the placebo cohort (rate ratio, 0.52; 95% CI, 0.36 to 0.73; P<0.001).

Across both trials, investigators did not observe a significant between-group difference in the change from baseline in the SGRQ score, as such they did not draw statistical inference on the trials’ secondary endpoints. In terms of safety, reports of adverse events (AEs) were similar across both cohorts in both trials.

In SWIFT-1, AEs were reported by 73% of patients in both cohorts, whereas in SWIFT-2, 72% of patients in the depemokimab cohort reported AEs compared to 78% of patients in the placebo cohort. No serious AEs or deaths were found to be related to depemokimab, according to the investigators.

“Our findings add to previous data showing that biologic therapies targeting interleukin-5 or its receptor (e.g., mepolizumab, reslizumab, and benralizumab) improve patient outcomes,” the study authors wrote. “Previous phase 3 trials of biologic therapies have shown reductions in the frequency of exacerbations in patients with asthma ranging from 17 to 59%, as evaluated in different patient populations and with dosing schedules ranging from 4 to 8 weeks. Our findings regarding depemokimab represent a potential advance in patient quality of life because therapies that have a reduced dosing frequency are associated with a lower patient-reported treatment burden in those with long-term conditions, along with an expected reduction in health care use.”¹

References

1. Jackson D., et al. Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. N Engl J Med 2024;391:2337-2349. DOI: 10.1056/NEJMoa2406673. Vol. 391 No. 24.

2. Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-1). ClinicalTrials.gov. Updated December 17, 2024. Accessed December 18, 2024. https://clinicaltrials.gov/study/NCT04719832

3. A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-2). ClinicalTrials.gov. Updated November 29, 2024. Accessed December 18, 2024. https://clinicaltrials.gov/study/NCT04718103

4. GSK announces positive results from phase III severe asthma trials of depemokimab. News release. GSK. May 21, 2024. Accessed December 18, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-positive-results-from-phase-iii-severe-asthma-trials-of-depemokimab/