Trial results for a Phase 3 study evaluating depemokimab (GSK3511294) in participants with severe asthma with an eosinophilic phenotype were posted on ClinicalTrials.gov on 2026-05-18. The study aimed to demonstrate non-inferiority of depemokimab compared to mepolizumab or benralizumab, with the primary analysis showing a rate ratio of 1.16 (95% CI: 0.98, 1.38) and a p-value of 0.079 for annualized clinically significant exacerbations.
Background
This study investigated depemokimab (GSK3511294) in participants with severe asthma with an eosinophilic phenotype. The trial assessed whether switching patients who had benefited from existing treatments like mepolizumab or benralizumab to depemokimab would maintain similar efficacy in reducing asthma exacerbations.
Trial design
The Phase 3 study (NCT04718389) enrolled 1717 participants with severe asthma with an eosinophilic phenotype. The study's primary objective was to demonstrate the non-inferiority of depemokimab plus standard of care (SoC) compared with an active comparator (mepolizumab or benralizumab) plus SoC, as assessed by the annualized rate of clinically significant exacerbations over a 52-week intervention period. Participants continued their non-biologic baseline SoC asthma treatment throughout the study.
Key results
The primary analysis, which used a negative binomial model to assess non-inferiority of depemokimab compared to active comparator, reported a rate ratio of 1.16 (95% CI: 0.98, 1.38) for the annualized rate of clinically significant exacerbations over 52 weeks, with a p-value of 0.079.
- For the annualized rate of clinically significant exacerbations over 52 weeks, the least squares mean was 0.57 Exacerbation per participant per year for the depemokimab 100mg SC group, compared to 0.49 Exacerbation per participant per year for the mepolizumab 100 mg / benralizumab 30 mg SC group.
- The weighted mean change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score was -0.69 (Standard Error: 0.476) for depemokimab and -0.86 (Standard Error: 0.486) for the active comparator. The mean difference (final values) was 0.17 (95% CI: -0.85, 1.2).
- The weighted mean change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score was 0.03 (Standard Error: 0.026) for depemokimab and 0.06 (Standard Error: 0.026) for the active comparator. The mean difference (final values) was -0.03 (95% CI: -0.09, 0.02).
- The weighted mean change from baseline in pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) was -0.014 Liter (Standard Error: 0.0093) for depemokimab and -0.018 Liter (Standard Error: 0.0095) for the active comparator. The mean difference (final values) was 0.004 (95% CI: -0.016, 0.024).
What this means
The results of this Phase 3 study indicate that depemokimab did not statistically demonstrate non-inferiority to mepolizumab or benralizumab in reducing the annualized rate of clinically significant asthma exacerbations. The primary analysis yielded a rate ratio of 1.16 with a p-value of 0.079, suggesting that depemokimab may not be comparable to the active comparators in preventing exacerbations in this patient population. While other secondary outcomes such as SGRQ, ACQ-5, and FEV1 showed broadly similar changes from baseline between the groups, these were also not statistically superior for depemokimab. Clinicians and patients considering treatment options for severe asthma with an eosinophilic phenotype will need to weigh these results against the established efficacy of existing biologic therapies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04718389, titled "A Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype", were posted on 2026-05-18 on clinicaltrials.gov.