Rademikibart Treatment for Moderate-to-Severe Uncontrolled Asthma A Phase 2B Randomized Clinical Trial

Rationale: Rademikibart (formerly CBP-201) is an IL-4R alpha-targeting antibody. Objectives: We sought to evaluate rademikibart in adults with moderate-to-severe, persistent, uncontrolled asthma. Methods: In this global Phase 2b trial, 322 patients were randomized 1:1:1 to two rademikibart groups (150 mg or 300 mg every other week, after a 600-mg loading dose) or a placebo group; rademikibart or placebo was administered subcutaneously for 24 weeks. Measurements and Main Results: Prebronchodilator (trough) forced expiratory volume in 1 second (FEV1) at Week 12 (primary endpoint) improved with rademikibart at 150 mg and 300 mg: Least squares mean changes (95% confidence interval), above placebo, were 140 ml (44-236 ml; P = 0.005) and 189 ml (92-286 ml; P < 0.001), respectively. Prebronchodilator (trough) FEV1 improvements occurred rapidly during Week 1, were sustained through Week 24, and were greatest in patients with high baseline blood eosinophils (patients with >= 300 eosinophils/ml experienced placebo-adjusted FEV1 improvement at Week 24 of 420 ml [95% confidence interval = 239-600 ml] in the 300-mg group). Rapid and sustained statistically significant improvements were also observed in percent predicted FEV1 and Asthma Control Questionnaire score across 24 weeks. Through Week 24, proportions of patients with one or more exacerbations were 7.5% (150 mg) and 9.3% (300 mg) versus 16.7% (placebo). Eighty-eight percent of patients completed treatment. Treatment-emergent adverse events were generally similar to placebo, and no eosinophilia was observed. Injection site reactions were mostly mild. The most common treatment-emergent adverse events (10-12% of patients) were cough, coronavirus disease (COVID-19), and dyspnea. Conclusions: Rapid and sustained improvements in lung function and asthma control were gained across 24 weeks of rademikibart therapy. Clinical trial registered with www.clinicaltrials.gov (NCT 04773678).