Switching to Twice-Yearly Depemokimab in Severe Asthma

Key Takeaways

• In severe asthma, switching to depemokimab every 26 weeks was associated with low clinically significant exacerbation rates over 52 weeks, but the noninferiority criterion was not met.
• Health-related quality of life, asthma control, and lung function remained stable across the study period.
• Adverse events were comparable between groups, and most participants in both groups had no clinically significant exacerbation.

In the NIMBLE phase 3A trial, investigators tested twice-daily dosing of depemokimab in participants who had already shown clinical benefit on either mepolizumab or benralizumab. Participants switched to depemokimab every 26 weeks or continued prior biologic therapy over 52 weeks.

NIMBLE was a multicenter, randomized, double-blind, double-dummy, parallel-group, phase 3A noninferiority study identified as NCT04718389. Eligible participants were aged 12 years or older and had severe asthma with documented clinical benefit on prior biologic therapy (mepolizumab 100 mg every 4 weeks or benralizumab 30 mg every 8 weeks) for at least 12 months. Investigators randomized participants 1:1 to depemokimab 100 mg subcutaneously every 26 weeks or to continuation of their prior biologic.

The primary endpoint was the annualized rate of clinically significant exacerbations over 52 weeks, with a prespecified noninferiority margin of 1.28. Annualized exacerbation rates were 0.57 with depemokimab and 0.49 with active comparator. The corresponding 95% CIs were 0.50 to 0.64 and 0.43 to 0.55, and sample sizes were 848 and 839, respectively. The rate ratio was 1.16, with a 95% CI of 0.98 to 1.38, so noninferiority was not met because the upper bound exceeded 1.28. Most participants in both groups had no clinically significant exacerbation.

Beyond exacerbations, health-related quality of life, asthma control, and lung function remained stable throughout the study. Adverse events were comparable between treatment groups. Across the one-year follow-up, symptom control and lung function were maintained, with similar safety reporting across groups.

The authors concluded that statistical noninferiority was not shown, even though exacerbation rates were low in both groups over 52 weeks. Symptom control and lung function were maintained in participants who switched and in those who continued prior therapy.