Early and Sustained Depemokimab Efficacy in Type 2 Asthma
Key Takeaways
- Depemokimab was associated with fewer first exacerbations than placebo over 52 weeks, and benefit appeared by week 4.
- Improvements were reported across each 26-week dosing period in symptom and quality-of-life measures, with sustained rescue medication improvement.
- Larger annualized exacerbation rate reductions were reported in patients with shorter asthma duration, chronic rhinosinusitis with nasal polyps, and medium-dose ICS use at baseline.
The pooled phase III result corresponded to a hazard ratio of 0.54, with a 95% CI of 0.43 to 0.69. Benefit was evident from week 4 with dosing every 26 weeks, and the effect was maintained across both 26-week treatment periods. The twice-yearly schedule remained associated with an effect visible through the full year of follow-up in the pooled population.
Background information described depemokimab as an ultralong-acting biologic that enables twice-yearly dosing in asthma. It also noted a 54% reduction in annualized exacerbation rate versus placebo in phase III SWIFT-1/-2, framing this pooled assessment of onset and durability. The pooled analysis enrolled adults with type 2 asthma, randomized 2:1 to depemokimab 100 mg subcutaneously or placebo every 26 weeks for 52 weeks. Prespecified endpoints included time to first exacerbation, St George's Respiratory Questionnaire or ACQ-5 scores, weekly daytime or nighttime symptom diary scores, and rescue medication use over time. That 52-week, twice-yearly schedule provided the basis for assessing both week 4 onset and durability across the two dosing periods.
Outcomes separated by week 4, and that pattern remained evident across each 26-week dosing interval. Across both periods, depemokimab was linked to better St George's Respiratory Questionnaire or ACQ-5 scores and Asthma Nighttime Symptom Diary or Asthma Daytime Symptom Diary results than placebo. These improvements were particularly noted among patients with baseline ACQ-5 scores of 1.5 or greater, although efficacy was evaluated independent of baseline ACQ-5 status. Rescue medication improvement was also sustained over time, reinforcing the consistency of symptom-related benefit through both dosing periods. These gains were observed across each dosing period rather than as a short-lived response after injection.
In post hoc subgroup analyses by baseline characteristics, annualized exacerbation rate reductions were most pronounced in three named groups. Those groups included patients with asthma duration under 10 years, chronic rhinosinusitis with nasal polyps, and medium-dose ICS use at baseline. The authors concluded that early and sustained efficacy was observed across 26-week dosing periods in type 2 asthma. The abstract highlighted those subgroup characteristics. They also linked enhanced benefit to shorter disease duration in patients who had not progressed to high-dose ICS.