Depemokimab Indirect Comparison Shows Similar Asthma Exacerbation Reduction

Key Takeaways

• In the fully adjusted model, depemokimab was associated with lower annualized exacerbation rates than placebo, while adjusted comparisons with other biologics were not statistically significant.
• Exacerbation estimates came from 17 trials and safety estimates came from 22 trials, using network meta-analysis and multi-level network meta-regression with covariate adjustment.
• Adverse-event and serious-adverse-event odds were similar across treatments, and fewer serious adverse events were observed with depemokimab than with dupilumab.

Across 17 trials in a depemokimab indirect treatment comparison, depemokimab significantly lowered annualized exacerbation rates versus placebo in the fully adjusted fixed-effect model. After adjustment, differences versus other biologics were not statistically significant. Covariate adjustment narrowed the comparative separation across biologics.

The analysis combined a systematic literature review with an indirect treatment comparison of randomized clinical trials of biologics in severe asthma. Endpoints were annualized exacerbation rates, adverse events, and serious adverse events. Investigators used unadjusted network meta-analysis followed by multi-level network meta-regression with partial and full adjustment for clinically relevant or statistically feasible covariates. Those covariates were prior exacerbation history, inhaled or oral corticosteroid use, and blood eosinophil count. The abstract also described depemokimab as the first ultra-long-acting biologic, and the adjustment strategy was central to how the comparative findings changed.

Efficacy results shifted as the models became more adjusted. In the unadjusted fixed-effect analysis, significant differences were observed versus placebo, omalizumab, benralizumab, and dupilumab 300 mg. In the partially adjusted fixed-effect model, significant differences remained versus placebo and omalizumab. In the fully adjusted fixed-effect model, the placebo comparison remained significant, but differences versus other biologics were no longer statistically significant. Results were generally consistent across fixed- and random-effect approaches.

Safety analyses drew on 22 trials. The odds of adverse events and serious adverse events were similar across treatments. Fewer serious adverse events were observed with depemokimab than with dupilumab. No additional safety differences were highlighted in the abstract. Safety findings were presented separately from the efficacy analyses.

The authors concluded that, overall, including after adjustment for clinically important patient characteristics, no statistically significant difference was detected between depemokimab and other severe asthma biologics for exacerbation reduction or safety. They characterized this as an indirect comparison rather than head-to-head evidence. The reported pattern was that adjustment reduced the apparent separation between depemokimab and comparator biologics.