Rademikibart for Asthma With Type 2 Biomarkers: Exploratory Subgroup Analyses From a Phase 2b Randomized Clinical Trial

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Abstract
Background: Rademikibart, an IL‐4Rα‐targeting antibody, demonstrated efficacy in a Phase 2b trial of adults with moderate‐to‐severe uncontrolled asthma (NCT04773678). We report exploratory and predominantly post hoc subgroup analyses, according to baseline eosinophil count (EOS) and fractional exhaled nitric oxide (FeNO). Methods: Patients were randomized, double‐blind, to rademikibart 150 mg or 300 mg Q2W (600‐mg loading) or placebo, with medium‐to‐high dose inhaled corticosteroids and ≥ 1 reliever/controller. Up to eight EOS/FeNO subgroups were investigated, focusing on the following five: ≥ 300 cells/μL and ≥ 25 ppb ( N = 80); ≥ 25 ppb ( N = 142); ≥ 300 cells/μL ( N = 129); ≥ 150 cells/μL ( N = 247); 150– < 300 cells/μL ( N = 118). Results: Prebronchodilator FEV 1 increased significantly at first assessment (Week 1) and was sustained throughout the 24‐week treatment period. FEV 1 and asthma control (ACQ‐6) improvements were greatest when baseline EOS and FeNO were both elevated. At Week 1, after a 600‐mg loading dose, placebo‐adjusted FEV 1 increased by 422 mL (≥ 300 cells/μL and ≥ 25 ppb), 339 mL (≥ 25 ppb), 324 mL (≥ 300 cells/μL), 227 mL (≥ 150 cells/μL), and 141 mL (150– < 300 cells/μL). At Week 24, with 300 mg Q2W, placebo‐adjusted FEV 1 increased by 519 mL (≥ 300 cells/μL and ≥ 25 ppb), 401 mL (≥ 25 ppb), 394 mL (≥ 300 cells/μL), 287 mL (≥ 150 cells/μL), and 159 mL (150– < 300 cells/μL). Exacerbations decreased by ≥ 63% per subgroup. Rademikibart was well tolerated. No eosinophilia (Preferred Term) was reported. Grade 1 eosinophil count increased did not lead to treatment discontinuation ( n = 2). Conclusions: Rapid and sustained improvements were more pronounced in patients with type 2‐high biomarkers than previously reported in the overall study population.

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