Early and Sustained Depemokimab Efficacy in Type 2 Asthma

Key Takeaways

• Depemokimab was associated with a 46% lower probability of first exacerbation over 52 weeks, with benefit reported from week 4 and sustained across both dosing periods.
• Improvements were also reported in St George's Respiratory Questionnaire, ACQ-5, Asthma Nighttime Symptom Diary, Asthma Daytime Symptom Diary, and rescue medication use during the dosing periods.
• Annualized exacerbation-rate reductions were most pronounced in patients with asthma duration under 10 years, chronic rhinosinusitis with nasal polyps, and medium-dose inhaled corticosteroid use at baseline.

In a pooled phase III SWIFT-1 and SWIFT-2 analysis of patients with type 2 asthma, depemokimab was associated with a 46% lower probability of first exacerbation than placebo over 52 weeks, with separation from placebo by week 4 that continued across both 26-week dosing periods.

Participants were 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 total score, ACQ-5 score, Asthma Nighttime Symptom Diary weekly score, Asthma Daytime Symptom Diary weekly score, and rescue medication use over time. These endpoints covered exacerbations, symptoms, quality of life, and rescue medication use.

For the primary time-to-event measure, depemokimab was associated with a hazard ratio of 0.54 for first exacerbation versus placebo, with a 95% confidence interval of 0.43 to 0.69. The effect appeared from week 4 and remained present across both 26-week dosing periods. Across each dosing period, depemokimab also improved St George's Respiratory Questionnaire, ACQ-5, Asthma Nighttime Symptom Diary, and Asthma Daytime Symptom Diary scores. Rescue medication use also improved across the study period.

Post hoc subgroup analyses by baseline characteristics showed the largest annualized exacerbation-rate reductions among patients with asthma duration under 10 years, comorbid chronic rhinosinusitis with nasal polyps, and medium-dose inhaled corticosteroid treatment at baseline. The pooled population was enrolled independent of baseline ACQ-5 status, while questionnaire and symptom-score improvements were particularly evident among patients with baseline ACQ-5 scores of 1.5 or greater.