Eosinophil Counts in Adults with Asthma Treated with Anti-IL-4Rα Rademikibart: Exploratory Analyses in a Randomized Trial.

Abstract

Eosinophil counts increased with IL-4Rα inhibition in Phase 3 trials. Rademikibart, a next-generation IL-4Rα inhibitor, resulted in rapid lung function improvements, sustained across 24 weeks of treatment, in adults with uncontrolled moderate-to-severe asthma during the CBP-201-WW002 Phase 2b trial. To investigate whether hypereosinophilia is a class (IL-4Rα inhibitor) effect, we analyzed eosinophil counts during treatment with rademikibart. As in previous Phase 3 trials of anti-IL-4Rα therapy, patients with eosinophil counts >1500 cells/μL at screening were excluded from this Phase 2b trial of rademikibart. Blood eosinophil counts were analyzed in 322 patients randomized to rademikibart 150 mg or 300 mg every two weeks (following a 600-mg loading dose) versus placebo. The study comprised of 24-week treatment and 8-week follow-up periods. In rademikibart 150 mg, 300 mg, and placebo groups, respectively, mean eosinophil counts (268, 320, and 299 cells/μL at baseline) changed by -8, -25, and 2 cells/μL at Week 12 and by -30, -97, and -23 cells/μL at Week 24. In a post hoc analysis of patients with ≥500 cells/μL at baseline, >1500 cells/μL were experienced by 10.0% (n = 3) of rademikibart-treated patients vs 18.8% (n = 3) with placebo. In patients with <500 cells/μL at baseline, >1500 cells/μL were experienced by 1.1% (n = 2) of rademikibart-treated patients vs 1.1% (n = 1) with placebo. One patient experienced >3000 cells/μL, during off-treatment follow-up (rademikibart 150 mg group). Two patients (rademikibart 300 mg group) experienced non-serious Grade 1 treatment-emergent adverse events (TEAEs) of 'eosinophil count increased' (n = 2) and 'eosinophil percentage increased' (n = 1). No clear differences occurred in infection or cardiovascular TEAEs per treatment group. Exploratory analyses suggest that rademikibart therapy may not result in hypereosinophilia, although larger confirmatory analyses are required. ClinicalTrials.gov, NCT04773678.