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

Abstract

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). 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). Prebronchodilator FEV₁ increased significantly at first assessment (Week 1) and was sustained throughout the 24-week treatment period. FEV₁ 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 FEV₁ 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 FEV₁ 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). Rapid and sustained improvements were more pronounced in patients with type 2-high biomarkers than previously reported in the overall study population.