Purpose To characterize the clinical phenotypes of severe eosinophilic asthma based on early responsiveness to benralizumab in terms of forced expiratory volume in 1 second (FEV.sub.1) improvement. Patients and methods Sixty-four participants diagnosed with severe eosinophilic asthma and who had completed 4 months of benralizumab treatment were included in this analysis. Pre-treatment clinical factors were compared between responders and non-responders according to improvements in ACT or FEV.sub.1 . Correlations between the sums of increased Type 2-related inflammatory parameters and changes of ACT or FEV.sub.1 were also evaluated before and after the 4-month treatment. A two-step cluster analysis was performed to identify distinct phenotypes related to benralizumab responsiveness in terms of FEV.sub.1. Results At the 4-month timepoint, all parameters, except for FeNO, were significantly improved after benralizumab treatment. FEV.sub.1 responders were associated with higher levels of Type 2-related inflammatory parameters. An improvement in FEV.sub.1 but not in ACT was clearly associated with increases in the sums of increased type 2-related inflammation parameters (p = 0.0001). The cluster analysis identified 5 distinct phenotypes of severe eosinophilic asthma according to the variable FEV.sub.1 responsiveness to benralizumab. The greatest response was found in the distinct phenotype of severe eosinophilic asthma, which was characterized by modest increase in total IgE and FeNO relative to blood eosinophils with least exposure to smoking. Conclusion This study, to the best of our knowledge, is the first cluster analysis to report distinct phenotypes related to clinical benralizumab response in a real-world population with severe eosinophilic asthma. These results may help to predict responsiveness to benralizumab in patients with severe eosinophilic asthma.