Eosinophil Counts in Adults With Asthma Treated with Anti-IL-4Rα Rademikibart

BACKGROUND: 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. RESEARCH QUESTION: Is treatment-emergent hypereosinophilia a class effect of IL-4Rα inhibition, or does it differ with rademikibart? STUDY DESIGN AND METHODS: As in previous phase 3 trials of anti-IL-4Rα therapy, patients with eosinophil counts > 1,500 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 or 300 mg every 2 weeks (after a 600-mg loading dose) vs placebo. The study included 24-week treatment and 8-week follow-up periods. RESULTS: 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, > 1,500 cells/μL were experienced by 10.0% of patients treated with rademikibart (n = 3) vs 18.8% of patients treated with placebo (n = 3). In patients with < 500 cells/μL at baseline, > 1,500 cells/μL were experienced by 1.1% of patients treated with rademikibart (n = 2) vs 1.1% of patients treated with placebo (n = 1). One patient experienced > 3,000 cells/μL during off-treatment follow-up (rademikibart 150-mg group). Two patients (rademikibart 300-mg group) experienced nonserious grade 1 treatment-emergent adverse events of eosinophil count increased (n = 2) and eosinophil percentage increased (n = 1). No clear differences occurred in infection or cardiovascular treatment-emergent adverse events per treatment group. INTERPRETATION: Exploratory analyses suggest that rademikibart therapy may not result in hypereosinophilia; however, larger confirmatory analyses are required. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04773678; URL: www. CLINICALTRIALS: gov.